gebhart/patrepeval huggingface dataset:
Mechanism of Mucosal Permeability Enhancement of CriticalSorb® (Solutol® HS15) Investigated In Vitro in Cell Cultures (2014)

Solutol® HS15 is the principle component of CriticalSorb™ that has shown an enhancement in permeability of medium sized biological drugs across epithelia. This study suggests that its mechanism of action arises primarily from effects on the cell membrane and consequent impacts on the cell cytoskeleton in terms of actin organisation and tight junction opening.
Solubility of Gases in Glass. II. He, Ne, and H2 in Fused Silica (1972)

The statistical thermodynamics of the gas-in-glass system provides a basic model of both physical and chemical solubility. The physical solubility result is essentially equivalent to that for monatomic solubility. The chemical solubility result is dependent upon the specific system involved. The model was compared with experiment for a variety of systems. Helium and neon in fused silica were examples of the physical solubility of monatomic gases. Variations of the thermal history of the fused silica did not appear to have a measurable effect on physical solubility as evidenced in the helium data. Hydrogen in fused silica was an example of the physical solubility of polyatomic gases. Physical solubility was measured by a modified Seiverts technique and was characterized by a linear dependence on pressure. Binding energies for the physically dissolved species were of the order expected for van der Waals bonding. Vibrational frequencies were on the order of 1013 sec−1 with the heavier species having the lower frequencies. Hydrogen in fused silica was also an example of the chemical solubility of polyatomic gases. The literature gave data for the chemical solution of hydrogen in fused silica, but the fused silica of this study did not, perhaps because of the presence of water-produced hydroxyls. Comparison of the model with the literature data showed a p1/2 pressure dependence for the solubility (indicative of dissociation) and a binding energy of about 63 kcal/mole (indicative of chemical bonding).
A Data-Driven Sparse GLM for fMRI Analysis Using Sparse Dictionary Learning With MDL Criterion (2010)

We propose a novel statistical analysis method for functional magnetic resonance imaging (fMRI) to overcome the drawbacks of conventional data-driven methods such as the independent component analysis (ICA). Although ICA has been broadly applied to fMRI due to its capacity to separate spatially or temporally independent components, the assumption of independence has been challenged by recent studies showing that ICA does not guarantee independence of simultaneously occurring distinct activity patterns in the brain. Instead, sparsity of the signal has been shown to be more promising. This coincides with biological findings such as sparse coding in V1 simple cells, electrophysiological experiment results in the human medial temporal lobe, etc. The main contribution of this paper is, therefore, a new data driven fMRI analysis that is derived solely based upon the sparsity of the signals. A compressed sensing based data-driven sparse generalized linear model is proposed that enables estimation of spatially adaptive design matrix as well as sparse signal components that represent synchronous, functionally organized and integrated neural hemodynamics. Furthermore, a minimum description length (MDL)-based model order selection rule is shown to be essential in selecting unknown sparsity level for sparse dictionary learning. Using simulation and real fMRI experiments, we show that the proposed method can adapt individual variation better compared to the conventional ICA methods.
Polymer Dynamics in PEG-Silica Nanocomposites: Effects of Polymer Molecular Weight, Temperature and Solvent Dilution (2012)

The mechanical properties of particulate nanocomposites strongly depend upon the particle dispersion, as well as on the closely related properties in thin polymer films covering the particle surface. The length scale of such changes is relevant for the understanding of particle-particle interactions, which ultimately dominate the mechanical response. Using well-defined 44 nm diameter silica nanoparticles dispersed in poly(ethylene glycol), we focus on surface-induced changes in polymer dynamics. Using proton time-domain NMR, we distinguish three polymer phases of different mobility, i.e., a strongly adsorbed, solid-like fraction, a fraction with intermediate relaxation times and a highly mobile fraction. We explore how these fractions change as we vary polymer molecular weight from 300 to 20 000 and particle volume fraction up to 0.3. A multiple-quantum experiment enables a closer analysis of the mobile component which we show consists of two fractions, one resembling the bulk melt-like and another one showing network-like properties. We demonstrate that above a polymer molecular weight-dependent volume fraction, polymers form elastically active links between particles, resulting in the physical gelation observed in such systems. Our results provide a quantitative picture of network formation, which is described by the amount and length of network-like chains as well as heterogeneities in the polymer dynamics. We relate changes in polymer dynamics to particle microstructure obtained from small angle neutron scattering
Serum Antibody Responses after Intradermal Vaccination against Influenza (2004)

As compared with an intramuscular injection of full-dose influenza vaccine, an intradermal injection of a reduced dose resulted in similarly vigorous antibody responses among persons 18 to 60 years of age but not among those over the age of 60 years.
Use of a Phage Display Technique to Identify Potential Osteoblast Binding Sites Within Osteoclast Lacunae (2002)

There is a temporal coupling between the processes of bone resorption and bone formation in normal skeletal remodeling. That is, osteoblastic activity usually follows episodes of osteoclastic activity. However, what has not been universally appreciated is that there also is a spatial coupling between these processes. Bone formation only occurs in the immediate vicinity of the resorptive event. In this study, we describe a phage display technique that has been used to identify the mechanisms by which osteoblasts recognize components of the prior resorbed lacunar surface. Using a type V tartrate-resistant acid phosphatase (TRAP) as the bait and a random peptide M13 phage display library as the probe, we have identified specific sequences that show a very high affinity for TRAP. One of these peptides, designated clone 5, has a subnanomolar Kd for TRAP, interacts with TRAP in a Far-Western assay, binds exclusively to TRAP within osteoclast lacunae, is present in osteoblasts, and can effectively block osteoblast binding to resorption surfaces. The clone 5 peptide shows a high homology to glypican 4 (GPC4), a proteoglycan attachment receptor found in a number of cell types.
EGFR targeted nanobody–photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer (2016)

Photodynamic therapy (PDT) induces cell death through local light activation of a photosensitizer (PS) and has been used to treat head and neck cancers. Yet, common PS lack tumor specificity, which leads to collateral damage to normal tissues. Targeted delivery of PS via antibodies has pre-clinically improved tumor selectivity. However, antibodies have long half-lives and relatively poor tissue penetration, which could limit therapeutic efficacy and lead to long photosensitivity. Here, in this feasibility study, we evaluate at the pre-clinical level a recently introduced format of targeted PDT, which employs nanobodies as targeting agents and a water-soluble PS (IRDye700DX) that is traceable through optical imaging. In vitro, the PS solely binds to cells and induces phototoxicity on cells overexpressing the epidermal growth factor receptor (EGFR), when conjugated to the EGFR targeted nanobodies. To investigate whether this new format of targeted PDT is capable of inducing selective tumor cell death in vivo, PDT was applied on an orthotopic mouse tumor model with illumination at 1h post-injection of the nanobody-PS conjugates, as selected from quantitative fluorescence spectroscopy measurements. In parallel, and as a reference, PDT was applied with an antibody-PS conjugate, with illumination performed 24h post-injection. Importantly, EGFR targeted nanobody-PS conjugates led to extensive tumor necrosis (approx. 90%) and almost no toxicity in healthy tissues, as observed through histology 24h after PDT. Overall, results show that these EGFR targeted nanobody-PS conjugates are selective and able to induce tumor cell death in vivo. Additional studies are now needed to assess the full potential of this approach to improving PDT.
Factor Analysis and Least-Squares Curve-Fitting of Infrared Spectra: An Application to the Study of Phase Transitions in Organic Molecules (1984)

The significance of eigenvectors and eigenspectra used in factor analysis, the relation of least-squares coefficients to the concentration of individual components, and the role of difference spectrum in the least-squares method have been examined theoretically. The equivalence of factor analysis and least-squares curve-fitting has been established. Factor analysis and least-squares curve-fitting have been attempted on the Fourier transform Infrared spectra of nonadecane, nonadecane-d 2 , nonadecane-d 2 melt, and C 24 H 49 ,COOH, obtained as a function of temperature. Experimental results have been used to substantiate theoretical conclusions.
The Assay of Chymotrypsin in Stool as a Simple and Effective Test of Exocrine Pancreatic Activity in Cystic Fibrosis (1988)

The study evaluates two methods of assay of fecal chymotrypsin (titrimetric and spectrophotometric method) as an index of exocrine pancreatic function. The assay was performed on 101 control subjects and 128 cystic fibrosis (CF) patients by the first method, and 75 controls and 102 CF patients by the second method. CF subjects were subdivided into four groups based on pancreatic function: total pancreatic insufficiency in the first group, partial pancreatic insufficiency in the second group, normal pancreatic function in the third group, and pancreatic insufficiency plus enzymatic treatment in the fourth group. Fifty-four CF patients were examined in the first group, 27 in the second group, 19 in the third group, and 28 in the fourth group by the titrimetric method; 23, 25, 50, and 65, respectively by the spectrophotometric method. The spectrophotometric method was highly reproducible and more sensitive and specific. With such a method the assay on stool random sampling correlated with the duodenal output of chymotrypsin after hormonal stimulation as well as fecal output of 72 h. The test had sensitivity and specificity of 100% if referred to CF patients with total pancreatic insufficiency. It was calculated that CF patients with normal fecal chymotrypsin have a probability of 76% to have a normal pancreatic function and a probability of 24% to have a partially compromised pancreatic function. The assay separates distinctly CF patients with a fat absorption coefficient greater than 90% from those with a coefficient less than 90%. The test is proposed for current clinical use in diagnosis and treatment of pancreatic insufficiency in cystic fibrosis.
Magnetic Iron Oxide Nanoworms for Tumor Targeting and Imaging (2008)

The synthesis, in vitro, and in vivo behavior of tumor-homing magnetic nanoworms (NW) are described. The particles consist of a chainlike aggregation of iron oxide (IO) cores in a dextran coating. When conjugated with a tumor-targeting peptide, they interact more effectively with a tumor-based target in vitro relative to spherical nanoparticles. Untargeted NW display similar in vivo circulation times and enhanced passive accumulation in mouse xenograft tumors relative to untargeted spherical IO nanoparticles. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2008/adma200800004_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The effect of vagal stimulation on plasma insulin and glucose levels in the baboon* (1967)

1. The concentration of insulin in the blood of fifteen fasting baboons, anaesthetized with pentobarbitone sodium, was measured by a specific radio-immunoassay method.2. The mean resting concentration of insulin was: inferior vena cava (IVC) 22 muu./ml. and splenic vein (after splenectomy) 140 muu./ml.3. Subdiaphragmatic stimulation of the cut right vagal trunk (at 10 impulses/sec, duration 1.5 msec, for 10 min) produced a mean increase of 50% over resting levels in IVC insulin concentration and an increase in splenic vein insulin of 30% over resting levels.4. The mean resting level of blood glucose in splenic vein blood was 89.4mg%, that in IVC blood was 79.4mg%. The difference is significant (P < 0.005).5. Vagal stimulation did not alter these glucose levels, so that insulin release following vagal stimulation is not secondary to hyperglycaemia.6. The increased insulin secretion following vagal stimulation might be expected to produce hypoglycaemia. Its failure to do so is discussed.
Coefficient determination related to optical gain in erbium-doped silicon-rich silicon oxide waveguide amplifier (2002)

Gain-determining coefficients in Er-doped, nanocrystal-Si (nc-Si) sensitized silica waveguide amplifiers are investigated. Single-mode, Er-doped silica waveguides with nc-Si embedded in them were prepared by electron cyclotron resonance plasma-enhanced chemical vapor deposition of Er-doped a-Si:Ox (x&amp;lt;2) followed by a high-temperature anneal to precipitate nc-Si. Exciting the Er ions via nc-Si by pumping the waveguide from the top with the 477 nm line of an Ar laser resulted in an enhancement of the transmitted 1535 nm signal of up to 14 dB/cm, indicating a possible net gain of up to 7 dB/cm. From the dependence of the signal enhancement upon the pump power, an emission cross section of 2×10−19 cm2 at 1535 nm and an effective excitation cross section of ⩾10−17 cm2 at 477 nm is obtained.
Vector calculus, linear algebra, and differential forms: a unified approach (1999)

*Preliminaries*Vectors, Matrices, and Derivatives*Solving Equations*Higher Partial Derivatives, Quadratic Forms, and Manifolds*Integration*Lengths of Curves, Areas of Surfaces*Forms and Vector Calculus*Appendix A*Some Harder Proofs*Appendix B*Programs*Index
Identification of Important Regions in the Cytoplasmic Juxtamembrane Domain of Type I Receptor That Separate Signaling Pathways of Transforming Growth Factor-β (1996)

Proteins in the transforming growth factor-beta (TGF-beta) superfamily exert their effects by forming heteromeric complexes of their type I and type II serine/threonine kinase receptors. The type I and type II receptors form distinct subgroups in the serine/threonine kinase receptor family based on the sequences of the kinase domains and the presence of a highly conserved region called the GS domain (or type I box) located just N-terminal to the kinase domain in the type I receptors. Recent studies have revealed that upon TGF-beta binding several serine and threonine residues in the GS domain of TGF-beta type I receptor (T beta R-I) are phosphorylated by TGF-beta type II receptor (T beta R-II) and that the phosphorylation of GS domain is essential for TGF-beta signaling. Here we investigated the role of cytoplasmic juxtamembrane region located between the transmembrane domain and the GS domain of T beta R-I by mutational analyses using mutant mink lung epithelial cells, which lack endogenous T beta R-I. Upon transfection, wild-type T beta R-I restored the TGF-beta signals for growth inhibition and production of plasminogen activator inhibitor-1 (PAI-1) and fibronectin. A deletion mutant, T beta R-I/JD1(delta 150-181), which lacks the juxtamembrane region preceding the GS domain, bound TGF-beta in concert with T beta R-II and transduced a signal leading to production of PAI-I but not growth inhibition. Recombinant receptors with mutations that change serine 172 to alanine (S172A) or threonine 176 to valine (T176V) were similar to wild-type T beta R-I in their abilities to bind TGF-beta, formed complexes with T beta R-II, and transduced a signal for PAI-1 and fibronectin. Similar to T beta R-I/JD1 (delta 150-181), however, these missence mutant receptors were impaired to mediate a growth inhibitory signal. These observations indicate that serine 172 and threonine 176 of T beta R-I are dispensable for extracellular matrix protein production but essential to the growth inhibition by TGF-beta.
Mitochondrial Sensitivity and Altered Calcium Handling Underlie Enhanced NMDA-Induced Apoptosis in YAC128 Model of Huntington's Disease (2007)

Expansion of a CAG repeat in the Huntington's disease (HD) gene results in progressive neuronal loss, particularly of striatal medium-sized spiny neurons (MSNs). Studies in human HD autopsy brain tissue, as well as cellular and animal models of HD, suggest that increased activity of NMDA-type glutamate receptors and altered mitochondrial function contribute to selective neuronal degeneration. In this regard, the YAC128 mouse model, expressing full-length human huntingtin with 128 glutamine repeats, has been the focus of much interest. Although NMDA-induced apoptosis is enhanced in YAC128 MSNs, here we report that the initial steps in the death signaling pathway, including NMDA receptor (NMDAR) current and cytosolic Ca2+ loading, are similar to those observed in wild-type MSNs. In contrast, we found that the NMDAR-mediated Ca2+ load triggered a strikingly enhanced loss of mitochondrial membrane potential in YAC128 MSNs, suggesting that NMDAR signaling via the mitochondrial apoptotic pathway is altered. This effect was accompanied by impaired cytosolic Ca2+ clearance after removal of NMDA, a difference that was not apparent after high potassium-evoked depolarization-mediated Ca2+ entry. Inhibition of the mitochondrial permeability transition (mPT) reduced peak cytosolic Ca2+ and mitochondrial depolarization evoked by NMDA in YAC128 MSNs but not wild-type MSNs. Hence, in contrast to YAC models with moderate CAG expansions, the enhanced NMDA-induced apoptosis in YAC128 MSNs is predominantly determined by augmented mitochondrial sensitivity to Ca2+-induced activation of the mPT. These results suggest that the CAG repeat length influences the mechanism by which mHtt enhances NMDAR-mediated excitotoxicity.
Is alcohol required for effective pancreatic cyst ablation? The prospective randomized CHARM trial pilot study (2016)

This study revealed similar ablation rates between the alcohol ablation group and the alcohol-free arm and demonstrates the safety and feasibility of an alcohol-free ablation protocol. This pilot study suggests that alcohol may not be required for effective cyst ablation.
Noncontiguous regions in the extracellular domain of EGF receptor define ligand-binding specificity. (1991)

Murine epidermal growth factor (EGF) binds with approximately 250-fold higher binding affinity to the human EGF receptor (EGFR) than to the chicken EGFR. This difference in binding affinity enabled the identification of a major ligand-binding domain for EGF by studying the binding properties of various chicken/human EGFR chimera expressed in transfected cells lacking endogenous EGFR. It was shown that domain III of EGFR is a major ligand-binding region. Here, we analyze the binding properties of novel chicken/human chimera to further delineate the contact sequences in domain III and to assess the role of other regions of EGFR for their contribution to the display of high-affinity EGF binding. The chimeric receptors include chicken EGFR containing domain I of the human EGFR, chicken receptor containing domain I and III of the human EGFR, and two chimeric chicken EGFR containing either the amino terminal or the carboxy terminal halves of domain III of human EGFR, respectively. In addition, the binding of various human-specific anti-EGFR monoclonal antibodies that interfere with EGF binding is also compared. It is concluded that noncontiguous regions of the EGFR contribute additively to the binding of EGF. Each of the two halves of domain III has a similar contribution to the binding energy, and the sum of both is close to that of the entire domain III. This suggests that the folding of domain III juxtaposes sequences that together constitute the ligand-binding site. Domain I also provides a contribution to the binding energy, and the added contributions of both domain I and III to the binding energy generate the high-affinity binding site typical of human EGFR.
Regulation of beta-glucuronidase expression in transgenic tobacco plants by an A/T-rich, cis-acting sequence found upstream of a French bean beta-phaseolin gene. (1989)

A 0.8-kilobase fragment from the 5'-flanking region of a French bean beta-phaseolin gene yielded strong, temporally regulated, and embryo-specific expression of beta-glucuronidase (GUS) in transgenic tobacco plants, paralleling that found for the seed protein phaseolin [Sengupta-Gopalan, C., Reichert, N.A., Barker, R.F., Hall. T.C., and Kemp, J.D. (1985) Proc. Natl. Acad. Sci. USA 82, 3320-3324]. Gel retardation and footprinting assays using nuclear extracts from immature bean cotyledons revealed strong binding of nuclear proteins to an upstream region (-628 to -682) that contains two inverted A/T-rich motifs. Fusion of a 103-base pair fragment or a 55-base pair synthetic oligonucleotide containing these motifs to a minimal 35S promoter/GUS cassette yielded strong GUS expression in several tissues. A different pattern of GUS expression was obtained in immature embryos and germinating seedlings from the nominally constitutive, full-length, 35S promoter. Whereas GUS expression under the control of the 0.8-kilobase beta-phaseolin regulatory region is limited to immature embryos, expression from constructs containing the A/T-rich motifs is strongest in roots. These data, combined with S1 mapping, provide direct evidence that a plant upstream A/T-rich sequence that binds nuclear proteins can activate transcription in vivo. They also indicate that additional regulatory elements in the beta-phaseolin 5'-flanking region are required for embryo-specific gene expression.
Addition of Autotrophic Carbon Fixation Pathways to Increase the Theoretical Heterotrophic Yield of Acetate (2010)

Abstract The production of valuable biological products from sugars via fermentation is of importance in the chemical industry. One key parameter by which processes are evaluated is the product carbon yield on substrate. In the normal growth of heterotrophic organisms on fermentable sugars, some carbon is lost as CO2. In the production of acetate from hexose or pentose sugars, homoacetogens using the reductive acetyl CoA pathway have a theoretical yield of acetate on glucose of 3. We hypothesized that the addition of enzymes necessary for fixation of the lost CO2 would enhance the theoretical carbon yield of acetate in the dark in organisms without the reductive acetyl CoA pathway. Using computational flux balances of central metabolism of Escherichia coli, we show that the addition of the enzymes for the reductive pentose phosphate (Calvin Benson Bassham) cycle increases the theoretical yield of acetate from glucose or xylose. An even more significant increase in the theoretical carbon yield of acetate was obtained by adding the reactions for the reductive tricarboxylic acid cycle (rTCA), matching that of homoacetogens. However, addition of these pathways did not result in an increase in the theoretical yield of other excreted metabolites or biomass.