gebhart/patrepeval huggingface dataset:
Strategy for microbiome analysis using 16S rRNA gene sequence analysis on the Illumina sequencing platform (2011)

Understanding the identity and changes of organisms in the urogenital and other microbiomes of the human body may be key to discovering causes and new treatments of many ailments, such as vaginosis. High-throughput sequencing technologies have recently enabled discovery of the great diversity of the human microbiome. The cost per base of many of these sequencing platforms remains high (thousands of dollars per sample); however, the Illumina Genome Analyzer (IGA) is estimated to have a cost per base less than one-fifth of its nearest competitor. The main disadvantage of the IGA for sequencing PCR-amplified 16S rRNA genes is that the maximum read-length of the IGA is only 100 bases; whereas, at least 300 bases are needed to obtain phylogenetically informative data down to the genus and species level. In this paper we describe and conduct a pilot test of a multiplex sequencing strategy suitable for achieving total reads of > 300 bases per extracted DNA molecule on the IGA. Results show that all proposed primers produce products of the expected size and that correct sequences can be obtained, with all proposed forward primers. Various bioinformatic optimization of the Illumina Bustard analysis pipeline proved necessary to extract the correct sequence from IGA image data, and these modifications of the data files indicate that further optimization of the analysis pipeline may improve the quality rankings of the data and enable more sequence to be correctly analyzed. The successful application of this method could result in an unprecedentedly deep description (800,000 taxonomic identifications per sample) of the urogenital and other microbiomes in a large number of samples at a reasonable cost per sample.
The carbohydrate moiety of human platelet glycocalicin. (1983)

Glycocalicin, a predominant glycoprotein on the human platelet surface, has been purified from a platelet suspension by sonication, ammonium sulfate precipitation and acid treatment followed by chromatography on columns of wheat germ agglutinin-Sepharose and Sephacryl S-300. Ser/Thr-linked (O-linked) oligosaccharides were released by alkaline borohydride treatment, and fractionated by high performance liquid chromatography with an anion-exchange resin. The structure of a major oligosaccharide alditol separated by high performance liquid chromatography was investigated by a combination of compositional analyses, methylation and glycosidase treatments, and proposed to be a hexasaccharide alditol, NeuAc alpha 2-3Gal beta 1-4GlcNAc beta 1-6(NeuAc alpha 2-3Gal beta 1-3) N-acetylgalactosaminitol. We also found some sugar units which appeared to be intermediates in the biosynthetic pathway of the major hexasaccharide.
Selection, affinity maturation, and characterization of a human scFv antibody against CEA protein (2006)

The binding affinity of the scFv E8 is in a range for efficient, in vivo, antigen capture in tumor cells expressing a shared epitope of the CEACAM1, 3 and 5 proteins. This new immunoreagent meets all criteria for a potential anticancer compound: it is human, hence poorly or not at all immunogenic, and it binds selectively and with good affinity to the CEA epitope expressed by metastatic melanoma and colon and lung carcinomas. Furthermore, its small molecular size should provide for efficient tissue penetration, yet give rapid plasma clearance.
Improved base calling for the Illumina Genome Analyzer using machine learning strategies (2009)

The Illumina Genome Analyzer generates millions of short sequencing reads. We present Ibis (Improved base identification system), an accurate, fast and easy-to-use base caller that significantly reduces the error rate and increases the output of usable reads. Ibis is faster and more robust with respect to chemistry and technology than other publicly available packages. Ibis is freely available under the GPL from http://bioinf.eva.mpg.de/Ibis/.
Serial Next-Generation Sequencing of Circulating Cell-Free DNA Evaluating Tumor Clone Response To Molecularly Targeted Drug Administration (2015)

Targeted NGS of cfDNA has potential clinical utility to monitor the delivery of targeted therapies.
Proton Transfer and Proton Concentrations in Protonated Nafion Fuel Cell Membranes (2009)

Proton transfer in protonated Nafion fuel cell membranes is studied using several pyrene derivative photoacids. Proton transfer in the center of the Nafion nanoscopic water channels is probed with the highly charged photoacid 8-hydroxypyrene-1,3,6-trisulfonate (HPTS). At high hydration levels, both the time-integrated fluorescence spectrum and the fluorescence kinetics of HPTS permit the determination of hydronium concentration of the interior of the water pools in Nafion. The proton transfer kinetics of HPTS in protonated Nafion at maximum hydration are identical to the kinetics displayed by HPTS in a 0.5 M HCl solution. The hydronium concentration near the water interface in Nafion is estimated with rhodamine-6G to be 1.4 M. Excited state proton transfer (ESPT) is followed in the nonpolar side chain regions of Nafion with the photoacid 8-hydroxy-N,N,N',N',N'',N''-hexamethylpyrene-1,3,6-trisulfonamide (HPTA). Excited state proton transfer of HPTA is possible in protonated Nafion only at the highest hydration level due to a relatively high local pH.
High‐Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging (2008)

The desire to improve and expand the scope of clinical magnetic resonance imaging (MRI) has prompted the search for contrast agents of higher efficiency. The development of better agents requires consideration of the fundamental coordination chemistry of the gadolinium(III) ion and the parameters that affect its efficacy as a proton relaxation agent. In optimizing each parameter, other practical issues, such as solubility and in vivo toxicity, must also be addressed, making the attainment of safe, high-relaxivity agents a challenging goal. This Minireview presents recent advances in the field, with an emphasis on gadolinium(III) hydroxypyridinone chelate complexes.
A novel non-radioactive cellular cytotoxicity test based on the differential assessment of living and killed target and effector cells (1995)

Monocyte/macrophage-mediated cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC) are slow processes, requiring cocultivation of effector and target cells for up to several days. Because of the high spontaneous release and possible reutilization of isotopic labels, the conventional radioactive release assays are unsuited for measuring long term cytotoxicity. We developed a non-radioactive flow cytometric assay for the quantitative analysis of cell-mediated cytotoxicity. Because dead cells can dissolve and disappear during the incubation period (lysis, phagocytosis), we determined the absolute numbers of living cells in the well. Prior to incubation the effector cells are stained with the red lipophilic fluorescent dye PKH26 and the target cells with the green fluorescent dye PKH2. At the end of the incubation (1-6 days) a defined number of bright fluorescent cell standards and propidium iodide for staining of dead cells was added to each well. Using flow cytometric analysis, we determined the ratio of targets to standards and calculated the absolute target cell number by multiplication with the known number of standards added. The main advantages of the assay are the possibility of extended incubation periods, the avoidance of radioactivity and its potential applicability to autologous culture systems, where effector and tumor cells are derived from the same patient. The assay opens new avenues for preclinical testing of tumor therapeutics such as monoclonal antibodies and/or cytokines.
Branched-chain amino acids prevent hepatic fibrosis and development of hepatocellular carcinoma in a non-alcoholic steatohepatitis mouse model (2017)

Oral supplementation with branched-chain amino acids (BCAA; leucine, isoleucine, and valine) in patients with liver cirrhosis potentially suppresses the incidence of hepatocellular carcinoma (HCC) and improves event-free survival. However, the detailed mechanisms of BCAA action have not been fully elucidated. BCAA were administered to atherogenic and high-fat (Ath+HF) diet-induced nonalcoholic steatohepatitis (NASH) model mice. Liver histology, tumor incidence, and gene expression profiles were evaluated. Ath+HF diet mice developed hepatic tumors at a high frequency at 68 weeks. BCAA supplementation significantly improved hepatic steatosis, inflammation, fibrosis, and tumors in Ath+HF mice at 68 weeks. GeneChip analysis demonstrated the significant resolution of pro-fibrotic gene expression by BCAA supplementation. The anti-fibrotic effect of BCAA was confirmed further using platelet-derived growth factor C transgenic mice, which develop hepatic fibrosis and tumors. In vitro, BCAA restored the transforming growth factor (TGF)-β1-stimulated expression of pro-fibrotic genes in hepatic stellate cells (HSC). In hepatocytes, BCAA restored TGF-β1-induced apoptosis, lipogenesis, and Wnt/β-Catenin signaling, and inhibited the transformation of WB-F344 rat liver epithelial stem-like cells. BCAA repressed the promoter activity of TGFβ1R1 by inhibiting the expression of the transcription factor NFY and histone acetyltransferase p300. Interestingly, the inhibitory effect of BCAA on TGF-β1 signaling was mTORC1 activity-dependent, suggesting the presence of negative feedback regulation from mTORC1 to TGF-β1 signaling. Thus, BCAA induce an anti-fibrotic effect in HSC, prevent apoptosis in hepatocytes, and decrease the incidence of HCC; therefore, BCAA supplementation would be beneficial for patients with advanced liver fibrosis with a high risk of HCC.
Imiquimod 5% cream for the treatment of superficial basal cell carcinoma: results from a randomized vehicle-controlled phase III study in Europe (2005)

Imiquimod 5% cream administered 7 x/week for 6 weeks is a safe and effective treatment for sBCC when compared with vehicle cream.
Systematic guide to complex cases from adhesive disease (2007)

Intestinal adhesions are inevitable after abdominal surgery. The presence of intra-abdominal adhesions can create very complex situations which require careful preoperative planning, meticulous intra-operative technique and detailed postoperative management. This manuscript will review the management of these complex cases of adhesions.
Characterization of Lipid Nanoparticles Containing Ionizable Cationic Lipids Using Design-of-Experiments Approach (2021)

Lipid nanoparticles (LNPs) containing short-interfering RNA (LNP-siRNA systems) are a promising approach for silencing disease-causing genes in hepatocytes following intravenous administration. LNP-siRNA systems are generated by rapid mixing of lipids in ethanol with siRNA in aqueous buffer (pH 4.0) where the ionizable lipid is positively charged, followed by dialysis to remove ethanol and to raise the pH to 7.4. Ionizable cationic lipids are the critical excipient in LNP systems as they drive entrapment and intracellular delivery. A recent study on the formation of LNP-siRNA systems suggested that ionizable cationic lipids segregate from other lipid components upon charge neutralization to form an amorphous oil droplet in the core of LNPs. This leads to a decrease in intervesicle electrostatic repulsion, thereby engendering fusion of small vesicles to form final LNPs of increased size. In this study, we prepared LNP-siRNA systems containing four lipid components (hydrogenated soy phosphatidylcholine, cholesterol, PEG-lipid, and 1,2-dioleoyl-3-dimethylammonium propane) by microfluidic mixing. The effects of preparation parameters [lipid concentration, flow rate ratio (FRR), and total flow rate], dialysis process, and complex formation between siRNA and ionizable cationic lipids on the physicochemical properties [siRNA entrapment on the particle size and polydispersity index (PDI)] were investigated using a design of experiments approach. The results for the preparation parameters showed no impact on siRNA encapsulation, but lipid concentration and FRR significantly affected the particle size and PDI. In addition, the effect of FRR on the particle size was suppressed in the presence of anionic polymers such as siRNA as compared to the case of LNPs alone. More intriguingly, unlike empty LNPs, a decrease in the PDI and an increase in the particle size occurred after dialysis in the LNP-siRNA systems. Such changes by dialysis were suppressed at FRR = 1. These findings provide useful information to guide the development and manufacturing conditions for LNP-siRNA systems.
Twisted Intramolecular Charge Transfer State for Long-Wavelength Thermally Activated Delayed Fluorescence (2013)

Emission wavelength tuning of thermally activated delayed fluorescence from green to orange in solid state films is demonstrated. Emission tuning occurs by stabilization of the intramolecular charge transfer state between a phenoxazine (PXZ) donor unit and 2,4,6-triphenyl-1,3,5-triazine (TRZ) acceptor unit separated by a large twist angle. The emission wavelengths of mono-, bis-, and tri-PXZ-substituted TRZ exhibit a gradual red shift while maintaining a small energy gap between the singlet and triplet excited states. An organic light-emitting diode containing a tri-PXZ-TRZ emitter exhibited a maximum external quantum efficiency of 13.3 ± 0.5% with yellow-orange emission.
Intrinsic and environmental response pathways that regulate root system architecture (2005)

Root system development is an important agronomic trait. The right architecture in a given environment allows plants to survive periods of water of nutrient deficit, and compete effectively for resources. Root systems also provide an optimal system for studying developmental plasticity, a characteristic feature of plant growth. This review proposes a framework for describing the pathways regulating the development of complex structures such as root systems: intrinsic pathways determine the characteristic architecture of the root system in a given plant species, and define the limits for plasticity in that species. Response pathways co-ordinate environmental cues with development by modulating intrinsic pathways. The current literature describing the regulation of root system development is summarized here within this framework. Regulatory pathways are also organized based on their specific developmental effect in the root system. All the pathways affect lateral root formation, but some specifically target initiation of the lateral root, while others target the development and activation of the lateral root primordium, or the elongation of the lateral root. Finally, we discuss emerging approaches for understanding the regulation of root system architecture.
Amino Acid Limitation Induces Expression of CHOP, a CCAAT/Enhancer Binding Protein-related Gene, at Both Transcriptional and Post-transcriptional Levels (1997)

In mammals, plasma concentrations of amino acids are affected by nutritional or pathological conditions. Here we examined the role of amino acid limitation in regulating the expression of CHOP, a CCAAT/enhancer binding protein (C/EBP)-related gene. CHOP protein is capable of interacting with other C/EBPs to modify their DNA binding activities and may function as a negative regulator of these transcription factors. Our data show that leucine limitation in human cell lines leads to induction of CHOP mRNA and protein in a dose-dependent manner. CHOP mRNA induction is rapidly reversed by leucine replenishment. Elevated mRNA levels result from both an increase in the rate of CHOP transcription and an increase in the CHOP mRNA stability. Using a transient expression assay, we show that a promoter fragment, when linked to a reporter gene, is sufficient to mediate the regulation of CHOP expression by leucine starvation in HeLa cells. In addition, we found that decreasing amino acid concentration by itself can induce CHOP expression independently of a cellular stress due to protein synthesis inhibition. Moreover, CHOP expression is induced at leucine concentrations in the range of those observed in blood of protein-restricted animals suggesting that amino acids can participate, in concert with hormones, in the regulation of gene expression.
Ruthenium Oxide-Carbon Composite Electrodes for Electrochemical Capacitors (1999)

For amorphous ruthenium, the current‐voltage characteristics of cyclic voltammetric (CV) curves depended strongly on the voltage scan rate. At high voltage scan rates, asymmetrical reduction and oxidation current behavior was obtained. The specific capacitance decreased with increasing voltage scan rate. The composite electrode was made by mixing ruthenium oxide powders and activated carbon black. The CV curve symmetry improved significantly at high voltage scan rates using composite electrodes, and the specific capacitance was less sensitive to the voltage scan rate. An electrochemical capacitor made with ruthenium oxide‐carbon composite electrodes demonstrated current densities as high as . ©1999 The Electrochemical Society
Fetal Vasculogenesis and Angiogenesis in Human Placental Villi (1989)

Placental villi of 5 exactly defined early human specimens ranging from day 21 post conception (p.c.) until day 42 p.c. and from an additional 43 specimens from about 5 to 40 weeks menstrual age have been analyzed ultrastructurally with regard to fetal vasculogenesis and angiogenesis. The following results were obtained: The first cells differentiating at day 21 p.c., probably originating from mesenchymal precursors, are macrophage-like cells. At almost the same time, mesenchymal cells transform into haemangioblastic cell cords which are the forerunners of the capillary endothelium and haematopoietic stem cells. A third cell population related to the fetal circulatory system and derived from the mesenchymal cells are presumptive pericytes. Capillary formation takes place by the aggregation of haemangioblastic cells which are attached to each other by intercellular junctions. The lumen is formed by the dehiscence of the intercellular clefts. A capillary basal lamina cannot be detected earlier than in the last trimester. In this last period of gestation, fetal villous angiogenesis takes place by the proliferation of the existing endothelium and pericytes rather than via haemangioblastic cells.
Pharmacologic consequences of cholesterol absorption inhibition: alteration in cholesterol metabolism and reduction in plasma cholesterol concentration induced by the synthetic saponin beta-tigogenin cellobioside (CP-88818; tiqueside). (1993)

Natural and synthetic saponins inhibit cholesterol absorption and reduce plasma cholesterol levels in experimental animals and are therefore of potential pharmacologic utility in the treatment of hypercholesterolemia. To determine the effects of this class of compounds on cholesterol absorption and metabolism, we evaluated the effects of the synthetic saponin, beta-tigogenin cellobioside (tiqueside; CP-88818), on male golden Syrian hamsters. When administered as either a single oral bolus or as a dietary supplement for up to 2 weeks, tiqueside inhibited cholesterol absorption in a dose-dependent manner in both the presence and absence of dietary cholesterol. Administration of tiqueside to chow-fed hamsters as a 0.2% dietary supplement (150 mg/kg per day) for 4 days resulted in a 68% decrease in intestinal cholesterol absorption with no change in either bile absorption or cholesterol 7 alpha-hydroxylase activity, suggesting that tiqueside inhibits cholesterol absorption without interfering with enterohepatic bile acid recirculation. Under these conditions, hepatic cholesterol levels were also reduced in a dose-dependent manner. Hepatic cholesterol reduction was highly correlated with cholesterol absorption inhibition, and induced compensatory increases in both hepatic HMG-CoA reductase activity and hepatic low density lipoprotein (LDL) receptor levels. Compensatory increases in intestinal HMG-CoA reductase activity were also noted after tiqueside administration, and are consistent with a luminal mechanism for tiqueside action. As a consequence of these changes to cholesterol metabolism, tiqueside administration induced plasma cholesterol reductions that were highly correlated with both hepatic cholesterol reduction and cholesterol absorption inhibition. Tiqueside also produced comparable plasma cholesterol lowering in a variety of other species fed either cholesterol-free diets (hamster, rat, mouse, dog) or cholesterol-containing diets (hamster, rat, rabbit, mouse, cynomolgus monkey, rhesus monkey, SEA quail) indicating the ubiquity of tiqueside action. For all species evaluated except the dog, the reduction in plasma cholesterol was due primarily to a reduction in circulating non-HDL cholesterol levels with little or no change in HDL cholesterol levels. Taken together, these results indicate that inhibition of cholesterol absorption by tiqueside produces profound effects on cholesterol metabolism without affecting bile acid metabolism, and that these changes lead to reductions primarily in plasma non-HDL cholesterol concentrations. The synthetic saponin, tiqueside, may thus represent a prototypical form of therapy for the treatment of hypercholesterolemia.
Suppression of human brain tumor with interference RNA specific for tenascin-C (2006)

Glioblastoma multiforme (GBM) accounts for approximately 12-15% of intracranial neoplasms. The GBM remains refractory to therapy because of tumor heterogeneity, local invasion, and non-uniform vascular permeability to drugs. Patients with GBM have the median survival of approximately 8-10 months, and for those cases where tumor recurs, the average time of tumor progression after therapy is only eight weeks. A combination of different treatment modes as surgery and chemo- or/and radiotherapy extend survival only for a short time, if any. Recently, tenascin-C (TN-C) as a dominant epitope in glioblastoma has been discovered. It is transiently expressed during organogenesis, absent or much reduced in most fully developed organs, but reappears under pathological conditions such as infection, inflammation, or tumorigenesis. It was found that the intensity of TN-C staining correlates with the tumor grade and that the strongest staining indicates poor prognosis.
Dendritic Cell Function in Vivo during the Steady State: A Role in Peripheral Tolerance (2003)

The avoidance of autoimmunity requires mechanisms to actively silence or tolerize self reactive T cells in the periphery. During infection, dendritic cells are not only capturing microbial antigens, but also are processing self antigens from dying cells as well as innocuous environmental proteins. Since the dendritic cells are maturing in response to microbial and other stimuli, peptides will be presented from both noxious and innocuous antigens. Therefore it would be valuable to have mechanisms whereby dendritic cells, prior to infection, establish tolerance to those self and environmental antigens that can be processed upon pathogen encounter. In the steady state, prior to acute infection and inflammation, dendritic cells are in an immature state and not fully differentiated to carry out their known roles as inducers of immunity. These immature cells are not inactive, however. They continuously circulate through tissues and into lymphoid organs, capturing self antigens as well as innocuous environmental proteins. Recent experiments have provided direct evidence that antigen-loaded immature dendritic in vivo silence T cells either by deleting them or by expanding regulatory T cells. In this way, it is proposed that the immune system overcomes at least some of the risk of developing autoimmunity and chronic inflammation. It is proposed that dendritic cells play a major role in defining immunologic self, not only centrally in the thymus but also in the periphery.