gebhart/patrepeval huggingface dataset:
Tube radial distribution phenomenon observed in an aqueous micellar solution of non-ionic surfactant fed into a microspace and an attempt of capillary chromatographic application (2013)

A new type of tube radial distribution phenomenon was observed in an aqueous micellar solution of non-ionic surfactant that was fed into a microspace. A homogeneous aqueous solution containing 2 wt % Triton X-100 and 2.0 M sodium chloride was fed into a microchannel (40 μm in depth and 200 μm in width) in a microchip at a flow rate of 4.0 μL/min, where the microchip was maintained at a temperature of 34°C. The homogeneous aqueous solution changed to a heterogeneous solution with two phases in the microchannel; the surfactant-rich phase was generated around the middle of the channel, while the aqueous phase containing little surfactant was formed near the wall. The radial distribution of the surfactant was observed through Rhodamine B dissolved in the aqueous micellar solution with a bright-field microscope — CCD camera system. An open-tubular capillary chromatographic system was also tried to develop using the fusedsilica capillary tube (75 μm inner diameter and 120 cm length) as a separation column and the aqueous micellar solution as a carrier.
BCL-2 Antagonism to Target the Intrinsic Mitochondrial Pathway of Apoptosis (2015)

Despite significant improvements in treatment, cure rates for many cancers remain suboptimal. The rise of cytotoxic chemotherapy has led to curative therapy for a subset of cancers, though intrinsic treatment resistance is difficult to predict for individual patients. The recent wave of molecularly targeted therapies has focused on druggable-activating mutations, and is thus limited to specific subsets of patients. The lessons learned from these two disparate approaches suggest the need for therapies that borrow aspects of both, targeting biologic properties of cancer that are at once distinct from normal cells and yet common enough to make the drugs widely applicable across a range of cancer subtypes. The intrinsic mitochondrial pathway of apoptosis represents one such promising target for new therapies, and successfully targeting this pathway has the potential to alter the therapeutic landscape of therapy for a variety of cancers. Here, we discuss the biology of the intrinsic pathway of apoptosis, an assay known as BH3 profiling that can interrogate this pathway, early attempts to target BCL-2 clinically, and the recent promising results with the BCL-2 antagonist venetoclax (ABT-199) in clinical trials in hematologic malignancies. See all articles in this CCR Focus section, "Cell Death and Cancer Therapy."
An alpha-particle emitting antibody ([213Bi]J591) for radioimmunotherapy of prostate cancer. (2000)

A novel alpha-particle emitting monoclonal antibody construct targeting the external domain of prostate-specific membrane antigen (PSMA) was prepared and evaluated in vitro and in vivo. The chelating agent, N-[2-amino-3-(p-isothiocyanatophen-yl)propyl]-trans-cyclohexane-1, 2-diamine-N,N',N',N'',N''-pentaacetic acid, was appended to J591 monoclonal antibody to stably bind the 213Bi radiometal ion. Bismuth-213 is a short-lived (t 1/2 = 46 min) radionuclide that emits high energy alpha-particles with an effective range of 0.07-0.10 mm that are ideally suited to treating single-celled neoplasms and micrometastatic carcinomas. The LNCaP prostate cancer cell line had an estimated 180,000 molecules of PSMA per cell; J591 bound to PSMA with a 3-nM affinity. After binding, the radiolabeled construct-antigen complex was rapidly internalized into the cell, carrying the radiometal inside. [213Bi]J591 was specifically cytotoxic to LNCaP. The LD50 value of [213Bi]J591 was 220 nCi/ml at a specific activity of 6.4 Ci/g. The potency and specificity of [213Bi]J591 directed against LNCaP spheroids, an in vitro model for micrometastatic cancer, also was investigated. [213Bi]J591 effectively stopped growth of LNCaP spheroids relative to an equivalent dose of the irrelevant control [213Bi]HuM195 or unlabeled J591. Cytotoxicity experiments in vivo were carried out in an athymic nude mouse model with an i.m. xenograft of LNCaP cells. [213Bi]J591 was able to significantly improve (P < 0.0031) median tumor-free survival (54 days) in these experiments relative to treatment with irrelevant control [213Bi]HuM195 (33 days), or no treatment (31 days). Prostate-specific antigen (PSA) was also specifically reduced in treated animals. At day 51, mean PSA values were 104 ng/ml +/- 54 ng/ml (n = 4, untreated animals), 66 ng/ml +/- 16 ng/ml (n = 6, animals treated with [213Bi]HuM195), and 28 ng/ml +/- 22 ng/ml (n = 6, animals treated with [213Bi]J591). The reduction of PSA levels in mice treated with [213Bi]J591 relative to mice treated with [213Bi]HuM195 and untreated control animals was significant with P < 0.007 and P < 0.0136, respectively. In conclusion, a novel [213Bi]-radiolabeled J591 has been constructed that selectively delivers alpha-particles to prostate cancer cells for potent and specific killing in vitro and in vivo.
The primary glucose-lowering effect of metformin resides in the gut, not the circulation: Results from short-term pharmacokinetic and 12-week dose-ranging studies (2020)

Delayed-release metformin (Met DR) is formulated to deliver the drug to the lower bowel to leverage the gut-based mechanisms of metformin action with lower plasma exposure. Met DR was assessed in two studies. Study 1 compared the bioavailability of single daily doses of Met DR to currently available immediaterelease metformin (Met IR) and extended-release metformin (Met XR) in otherwise healthy volunteers. Study 2 assessed glycemic control in subjects with type 2 diabetes (T2DM) over 12 weeks. Research Design and Methods Study 1 was a phase 1, randomized, four-period crossover study in 20 subjects. Study 2 was a 12-week, phase 2, multicenter, placebo-controlled, dose-ranging study in 240 subjects with T2DM randomized to receive Met DR 600, 800, or 1,000 mg administered once daily; blinded placebo; or unblindedMet XR 1,000 or 2,000 mg (reference). Results The bioavailability of 1,000mg Met DR b.i.d. was ∼50% that of Met IR and Met XR (study 1). In study 2, 600, 800, and 1,000 mg Met DR q.d. produced statistically significant, clinically relevant, and sustained reductions in fasting plasma glucose (FPG) levels over 12 weeks compared with placebo, with an ∼40% increase in potency compared with Met XR. The placebo-subtracted changes from baseline in HbA1c level at 12 weeks were consistent with changes in FPG levels. All treatments were generally well tolerated, and adverse events were consistent with Glucophage/ Glucophage XR prescribing information. Conclusions Dissociation of the glycemic effect from plasma exposure with gut-restricted Met DR provides strong evidence for a predominantly lower bowel-mediated mechanism of metformin action.
GaInNAs resonant-cavity-enhanced photodetector operating at 1.3 μm (1999)

We demonstrate a GaAs-based p-i-n resonant-cavity-enhanced (RCE) GaInNAs photodetector operating near 1.3 μm. The device design was optimized using a transfer matrix method and experimental absorption spectra obtained from p-i-n structures grown without a resonant cavity. The RCE photodetector was fabricated in a single growth step by using GaAs/AlAs distributed Bragg reflectors for the top and bottom mirrors. A 72% quantum efficiency was obtained with a full width at half maximum of 11 nm.
Insulin Increases Nuclear Protein Kinase Cδ in L6 Skeletal Muscle Cells (2007)

Protein kinase C (PKC) isoforms are involved in the transduction of a number of signals important for the regulation of cell growth, differentiation, apoptosis, and other cellular functions. PKC proteins reside in the cytoplasm in an inactive state translocate to various membranes to become fully activated in the presence of specific cofactors. Recent evidence indicates that PKC isoforms have an important role in the nucleus. We recently showed that insulin rapidly increases PKCdelta RNA and protein. In this study we initially found that insulin induces an increase in PKCdelta protein in the nuclear fraction. We therefore attempted to elucidate the mechanism of the insulin-induced increase in nuclear PKCdelta. Studies were performed on L6 skeletal myoblasts and myotubes. The increase in nuclear PKCdelta appeared to be unique to insulin because it was not induced by other growth factors or rosiglitazone. Inhibition of transcription or translation blocked the insulin-induced increase in nuclear PKCdelta, whereas inhibition of protein import did not. Inhibition of protein export from the nucleus reduced the insulin-induced increase in PKCdelta in the cytoplasm and increased it in the nucleus. The increase in nuclear PKCdelta induced by insulin was reduced but not abrogated by treatment of isolated nuclei by trypsin digestion. Finally, we showed that insulin induced incorporation of (35)S-methionine into nuclear PKCdelta protein; this effect was not blocked by inhibition of nuclear import. Thus, these results suggest that insulin may induce nuclear-associated, or possibly nuclear, translation of PKCdelta protein.
The C Terminus of the Nuclear RAN/TC4 GTPase Stabilizes the GDP-bound State and Mediates Interactions with RCC1, RAN-GAP, and HTF9A/RANBP1 (1995)

Ran/TC4 is a member of the Ras superfamily of GTPases. It is unusual in being predominantly nuclear and because it possesses an acidic -DEDDDL sequence instead of a consensus prenylation domain at the C terminus. Ran is required for nuclear protein import and cell cycle progression, and has been implicated in mRNA processing and export and DNA replication. The inhibition of cell cycle progression by a dominant gain-of-function mutant of Ran has been shown to be abrogated by removal of the -DEDDDL sequence, suggesting that this domain is essential for Ran function. We demonstrate here that the -DEDDDL sequence stabilizes GDP binding to Ran, and that the domain is required for high affinity interaction with a Ran-binding protein, HTF9A/RanBP1. HTF9A functions as a co-stimulator of Ran-GAP (GTPase activating protein) activity on wild-type Ran, but in the absence of the acidic C terminus of Ran, HTF9A behaves as a Ran-GAP inhibitor. An antibody directed against the C-terminal region preferentially recognizes the GTP-bound form of Ran, suggesting that this domain undergoes a nucleotide-dependent conformational change. The results suggest that the acidic C-terminal domain is important in modulating the interaction of Ran with regulatory factors, and implicate Ran-binding proteins in mediating the effects of Ran on cell cycle progression.
Effect of a lipid‐rich emollient containing ceramide 3 in experimentally induced skin barrier dysfunction (2002)

In the present study we compared the effect of a ceramide 3-containing emollient (Locobase(R) Repair) with a control emollient (vaselinum album/cremor lanette ana) and untreated damaged skin using clinical, bioengineering and immunohistochemical methods in two different models of experimentally induced skin barrier dysfunction. In model A (n = 13) skin barrier dysfunction was inflicted at three investigation sites by tape stripping. In model B (n = 13) the volunteers were patch tested at three investigation sites with sodium dodecyl sulphate (0.2%) for 4 h a day for 4 consecutive days. The investigation sites were treated once a day with the above-mentioned agents. Irritant reaction was assessed daily by erythema scoring and measurements of transepidermal water loss (TEWL). After 5D, punch biopsies were taken from all sites. Immunohistochemical assessment was carried out with respect to epidermal proliferation, epidermal differentiation and Langerhans cells. Tape stripping resulted in an erythematous reaction and an increase of TEWL associated with up-regulation of cycling cells, involucrin and expression of cytokeratin 16. At day 4, ceramide 3-containing emollient significantly decreased (p < 0.03) the erythema score, TEWL and cycling cells in comparison with the untreated site. Repetitive exposure to SDS induced a variable degree of erythema, gradual increase of TEWL, an increase of cycling cells, and up-regulation of involucrin, E-FABP and SKALP. The treatment with the control emollient significantly prevented erythema, increase of TEWL and cycling cells at day 4 compared to the untreated site. In summary, the present study demonstrated that both tested emollients improve skin barrier in different conditions compared to the untreated skin. There is some indication that formulations containing skin-related lipids might be of benefit in barrier disruption following tape stripping. Different models and clinical trials are needed to establish the usefulness in specific conditions of emollients containing skin-related lipids.
High-Throughput Screening for Functional Adenosine to Inosine RNA Editing Systems (2006)

Deamination of adenosines within messenger RNAs catalyzed by adenosine deaminases that act on RNA (ADAR) enzymes generates inosines at the corresponding nucleotide positions. Because inosine is decoded as guanosine, this reaction can lead to codon changes and the introduction of amino acids into a gene product not encoded in the gene. Translation of the different coding strands created by this process leads to protein structural diversity in the parent organism and is necessary for nervous system function in metazoa. The basis for selective editing of adenosines within certain codons is not well understood at the structural/biochemical level. Here we describe a high-throughput screen for ADAR/substrate combinations capable of RNA editing that can be carried out in the yeast Saccharomyces cerevisiae growing on agar plates. Results from the screening of libraries of human ADAR2 mutants and libraries of RNA substrates shed light on structure-activity relationships in the ADAR-catalyzed adenosine to inosine RNA editing reaction.
Polymerization-Induced Self-Assembly (PISA) – control over the morphology of nanoparticles for drug delivery applications (2013)

In this paper, we describe the synthesis of asymmetric functional POEGMA-b-P(ST-co-VBA) copolymers in methanol, yielding in one-pot polymerization a range of nanoparticle morphologies, including spherical micelles, worm-like, rod-like micelles and vesicles. The presence of the aldehyde group was then exploited to form crosslinks or to conjugate chemotherapy compounds, such as doxorubicin, via pH-breakable bonds (Schiff base or imine) directly to the preformed nanoparticles. The influence of the nanoparticle morphologies on the MCF-7 breast cancer cell line uptake was investigated using flow cytometry and confocal microscopy. Finally, the IC50 of DOX, following nanoparticle delivery, was studied showing significant influence of the nanoparticle carrier morphology on therapeutic efficacy for breast cancer.
Potential Implication of Endothelial Cells in Bronchial Asthma (1991)

Inflammatory cells like eosinophils, neutrophils or mononuclear phagocytes have long been recognized as essential components in the pathophysiology of asthma. After recruitment in situ and subsequent activation, they are considered as responsible for epithelial and submucosal bronchial alterations. However, to access to the inflammatory site, these cells have to cross the endothelial wall, suggesting so a potential implication of endothelial cells (EC) in bronchial asthma. To test this hypothesis, we studied in a first step the modulation of vascular adhesions like intercellular adhesion molecule-1 (ICAM-1) on EC: supernatants of alveolar macrophages (AM) recovered by bronchoalveolar lavage in patients exhibiting a late asthmatic reaction, induced an enhanced expression of ICAM-1 on EC preparations; increase of ICAM-1 was clearly correlated to amounts of tumor necrosis factor-alpha (TNF alpha) present in AM supernatants, as shown by inhibition experiments with anti-TNF alpha antiserum. The second way to explore the possible role of EC in asthma was the detection of autoantibodies to EC in various allergic disorders: antibodies against a 120-kD EC antigen in patients with allergic granulomatosis and angiitis, antibodies towards a 55-kD component, common to human EC and platelets in patients with severe asthma, namely characterized by their corticosteroid dependence or by aspirin-induced intolerance. So our data suggest that bronchial asthma might result from either EC activation, through the induction of surface adhesion molecules or from an autoimmune process involving EC antigens.
IL-17 and Th17 Cells in Atherosclerosis (2014)

Atherosclerosis is a chronic inflammatory arterial disease driven by both innate and adaptive immune responses to modified lipoproteins and components of the injured vascular wall. Specific T lymphocyte responses driven by T helper-1 or T regulatory cells play distinct and opposing roles in atherosclerosis. More recently, T helper-17 cells, which produce the prototype cytokine interleukin-17, have been characterized and shown to be critical in mucosal host defense against microbial and fungal pathogens. Sustained production of interleukin-17 in an inflammatory context has been linked to the pathology of several autoimmune and inflammatory diseases. However, regulatory and protective roles have also been reported in selective disease settings. Studies in atherosclerosis led to conflicting results on the roles of interleukin-17 and T helper-17 cells in disease development and plaque stability. The present review provides a summary of the available evidence and putative mechanisms linking this pathway to atherosclerosis, as well as a perspective on the risks and benefits of interleukin-17-targeted cytokine therapy in patients at high cardiovascular risk.
Mutational analysis of insertion sequence 50 (IS50) and transposon 5 (Tn5) ends. (1988)

Insertion sequence 50 (IS50) transposition utilizes a 19-base-pair "outside" end and a 19-base-pair "inside" end in inverted orientation relative to each other, whereas transposon 5 (Tn5) transposition utilizes two inverted outside ends. The frequency of transposition events that involve an inside end is regulated 1000-fold by the host dam methylase system. The end sequence requirements for transposition and its regulation by dam methylase were analyzed in Escherichia coli by generating random single base pair mutations in either an IS50 inside end or outside end placed in inverted orientation with respect to an unmutagenized outside end. The mutations were then isolated, assayed for transposition phenotype, and sequenced. Mutations were isolated at 15 of the 19 sites in the outside end. All of these mutations except those at position 4 decreased transposition. Mutations at position 4 (which is the only nonidentical base pair in a region of homology between the outside and inside ends) had no effect on transposition. Mutations were isolated at 11 of the 19 sites in the inside end. All of these mutations, including one at position 4, decreased transposition in dam- cells. Mutations at position 10 (within a dam recognition sequence) and 2 (not within a dam recognition sequence) reduced the magnitude of dam regulation. A mutation within a dam recognition sequence adjacent to the required 19 base pairs of the inside end did not reduce the magnitude of dam regulation.
Fas-ligand: Privilege and peril (1997)

Emotions coordinate our behavior and physiological states during survival-salient events and pleasurable interactions. Even though we are often consciously aware of our current emotional state, such as anger or happiness, the mechanisms giving ...Emotions are often felt in the body, and somatosensory feedback has been proposed to trigger conscious emotional experiences. Here we reveal maps of bodily sensations associated with different emotions using a unique topographical self-report method. In ...
Growth and fermentation of D-xylose by Saccharomyces cerevisiae expressing a novel D-xylose isomerase originating from the bacterium Prevotella ruminicola TC2-24 (2013)

This study identifies a new xylose isomerase from the rumen bacterium Prevotella ruminicola TC2-24 that has one of the highest affinities and specific activities compared to other bacterial and fungal D-xylose isomerases expressed in yeast. When expressed in S. cerevisiae and used to ferment D-xylose, very high ethanol yield was obtained. This new XI should be a promising resource for constructing other D-xylose fermenting strains, including industrial yeast genetic backgrounds.
Experiments with open-domain textual Question Answering (2000)

This paper describes the integration of several knowledge-based natural language processing techniques into a Question Answering system, capable of mining textual answers from large collections of texts. Surprizing quality is achieved when several lightweight knowledge-based NLP techniques complement mostly shallow, surface-based approaches.
A Systemic Small RNA Signaling System in Plants (2004)

Systemic translocation of RNA exerts non-cell-autonomous control over plant development and defense. Long-distance delivery of mRNA has been proven, but transport of small interfering RNA and microRNA remains to be demonstrated. Analyses performed on phloem sap collected from a range of plants identified populations of small RNA species. The dynamic nature of this population was reflected in its response to growth conditions and viral infection. The authenticity of these phloem small RNA molecules was confirmed by bioinformatic analysis; potential targets for a set of phloem small RNA species were identified. Heterografting studies, using spontaneously silencing coat protein (CP) plant lines, also established that transgene-derived siRNA move in the long-distance phloem and initiate CP gene silencing in the scion. Biochemical analysis of pumpkin (Cucurbita maxima) phloem sap led to the characterization of C. maxima Phloem SMALL RNA BINDING PROTEIN1 (CmPSRP1), a unique component of the protein machinery probably involved in small RNA trafficking. Equivalently sized small RNA binding proteins were detected in phloem sap from cucumber (Cucumis sativus) and lupin (Lupinus albus). PSRP1 binds selectively to 25-nucleotide single-stranded RNA species. Microinjection studies provided direct evidence that PSRP1 could mediate the cell-to-cell trafficking of 25-nucleotide single-stranded, but not double-stranded, RNA molecules. The potential role played by PSRP1 in long-distance transmission of silencing signals is discussed with respect to the pathways and mechanisms used by plants to exert systemic control over developmental and physiological processes.