gebhart/patrepeval huggingface dataset:
Melittin Enables Efficient Vesicular Escape and Enhanced Nuclear Access of Nonviral Gene Delivery Vectors (2001)

Entry of exogenously applied DNA into the cytoplasm and subsequent transport into the nucleus are major cellular barriers for nonviral gene delivery vectors. To overcome these barriers, we have covalently attached the cationic peptide melittin to poly(ethylenimine) (PEI). This conjugate condensed DNA into small, discrete particles (<100 nm in diameter), and the membrane lytic activity of melittin enabled efficient release of the DNA into the cytoplasm, as monitored by fluorescence microscopy and flow cytometry. Compared with PEI, the transfection activity was strongly increased within a broad range of cell lines and types tested, including different tumor cell lines but also primary hepatocytes and human umbilical vein endothelial cells. The early onset of gene expression (within 4 h, reaching maximal values after 12 h) and the high reporter gene expression achieved in slowly dividing or confluent cells suggested a further role of melittin after releasing the DNA into the cytoplasm. Intracytoplasmic microinjection of melittin-containing PEI.DNA complexes into fibroblasts produced 40% cellular frequency of reporter gene expression that was inhibitable by co-injection of wheat germ agglutinin, whereas simple PEI.DNA complexes showed only 10%. These data suggest that melittin enables release of nonviral gene transfer particles into the cytoplasm and also enhances their transport into the nucleus, possibly via the cationic cluster KRKR near the C terminus of the peptide.
The role of the endocannabinoid pathway in metabolism and diabetes (2006)

Purpose of review Exogenous and endogenous cannabinoids have for some time been known to exert a potent orexigenic effect. In the last couple of years, however, it has been shown that endocannabinoids not only modulate the functions of hypothalamic and mesolimbic centers involved in control of food intake, but also mediate metabolic functions, as demonstrated by their ability to target peripheral tissues such as adipose tissue, skeletal muscle and liver. Recent findings The recent publication of studies in humans in which rimonabant – the first compound of a new class of drugs able to antagonize the cannabinoid type 1 receptor – was demonstrated to efficiently tackle visceral obesity and related metabolic disorders confirmed the hypothesis that blockade of the endocannabinoid system may have beneficial effects by directly impacting on peripheral metabolic functions. Summary Future studies with this new class of drugs will shed further light on this issue, and the advent of this class of cannabinoid type 1 receptor antagonists will probably pave the way to a new era of pharmacotherapy for visceral obesity and related metabolic diseases.
Second-Generation Antipsychotic Drugs in Anorexia Nervosa: A Meta-Analysis of Randomized Controlled Trials (2015)

Background: Second-generation antipsychotic drugs (SGAs) are increasingly administered to achieve weight gain in anorexia nervosa. In this meta-analysis, we aimed to determine if any evidence for this treatment option can be derived from randomized controlled trials (RCTs). Methods: Based on the 'World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for the Pharmacological Treatment of Eating Disorders', a systematic update literature search was applied to identify all RCTs investigating the efficacy, acceptability, and tolerability of SGAs in anorexia nervosa in comparison to placebo/no treatment. The primary outcome was weight gain measured by mean change in body mass index (BMI). Secondary outcomes were mean changes in Yale-Brown-Cornell Eating Disorders Scale (YBC-EDS) total score and Eating Disorders Inventory (EDI) total score and premature discontinuation of treatment. Employing a random-effects model standardized mean differences based on Hedges's g and Mantel-Haenszel risk ratios were calculated. Results: Seven RCTs (n = 201) investigating olanzapine (N = 4), quetiapine (N = 2), and risperidone (N = 1) were included. We found no statistically significant between-group differences for mean BMI change when pooling the SGAs (N = 7, n = 161; Hedges's g = 0.13, 95% CI: -0.17 to 0.43; p = 0.4) and when examining the individual drugs. Furthermore, the SGAs failed to differentiate statistically significantly from placebo/no treatment for all secondary outcomes. Conclusions: Based on the current evidence, pharmacological treatment of anorexia nervosa with SGAs cannot be generally recommended although some individuals or subgroups of patients might benefit from an antipsychotic medication. Further research is required to identify which patients will likely benefit from such a treatment option. © 2015 S. Karger AG, Basel.
Subtilisin Novo. The Three-Dimensional Structure and Its Comparison with Subtilisin BPN' (1972)

1 The three-dimensional structure of subtilisin Novo was determined by X-ray crystallographic methods to a resolution of 0.28 nm and compared with the structure of subtilisin BPN′. 2 The two subtilisins have an equal amino acid sequence. It is shown that neither the quite different media nor the different lattice contacts in the two crystal forms result in any major structural change. 3 Subtilisin Novo has a binding site for monovalent cations.
Hematopoietic stem cells promote the expansion and function of adoptively transferred antitumor CD8+ T cells (2007)

Depleting host immune elements with nonmyeloablative regimens prior to the adoptive transfer of tumor-specific CD8(+) T cells significantly enhances tumor treatment. In the current study, superior antitumor efficacy was achieved by further increasing the intensity of lymphodepletion to a level that required HSC transplantation. Surprisingly, the HSC transplant and not the increased lymphodepletion caused a robust expansion of adoptively transferred tumor-specific CD8(+) T cells. The HSC-driven cell expansion of effector, but not of naive, CD8(+) T cells was independent of in vivo restimulation by MHC class I-expressing APCs. Simultaneously, HSCs also facilitated the reconstitution of the host lymphoid compartment, including inhibitory elements, not merely via the production of progeny cells but by enhancing the expansion of cells that had survived lymphodepletion. Profound lymphodepletion, by myeloablation or by genetic means, focused the nonspecific HSC boost preferentially toward the transferred tumor-specific T cells, leading to successful tumor treatment. These findings indicate that CD8(+) T cell-mediated tumor responses can be efficiently driven by HSCs in the myeloablative setting and have substantial implications for the design of new antitumor immunotherapies.
Binding-Induced DNA Assembly and Its Application to Yoctomole Detection of Proteins (2011)

We describe the binding-induced DNA assembly principle and strategy that enable ultrasensitive detection of molecular targets and potential construction of unique nanostructures/nanoreactors. Two DNA motifs that are conjugated to specific affinity ligands assemble preferentially only when a specific target triggers a binding event. The binding-induced assembly of the DNA motifs results in the formation of a highly stable closed-loop structure, raising the melting temperature (T(m)) of the hybrid by >30 °C and enabling effective differentiation of the target-specific assembly from the background. The ability to detect as few as a hundred molecules (yoctomole) of streptavidin, platelet derived growth factor, and prostate specific antigen represents an improvement of detection limits by 10(3)-10(5)-fold over traditional immunoassays. The assay is performed in a single tube, eliminating separation, immobilization, and washing steps of conventional assays. By incorporating unique signaling and structural features into the DNA motifs, we envision diverse applications in biosensing and nanotechnology.
Effects of tetrahydrofolate polyglutamates on the kinetic parameters of serine hydroxymethyltransferase and glycine decarboxylase from pea leaf mitochondria (1993)

Plant tissues contain highly conjugated forms of folate. Despite this, the ability of plant folate-dependent enzymes to utilize tetrahydrofolate polyglutamates has not been examined in detail. In leaf mitochondria, the glycine-cleavage system and serine hydroxymethyltransferase, present in large amounts in the matrix space and involved in the photorespiratory cycle, necessitate the presence of tetrahydrofolate as a cofactor. The aim of the present work was to determine whether glutamate chain length (one to six glutamate residues) influenced the affinity constant for tetrahydrofolate and the maximal velocities displayed by these two enzymes. The results show that the affinity constant decreased by at least one order of magnitude when the tetrahydrofolate substrate contained three or more glutamate residues. In contrast, maximal velocities were not altered in the presence of these substrates. These results are consistent with analyses of mitochondrial folates which revealed a pool of polyglutamates dominated by tetra and pentaglutamates. The equilibrium constant of the serine hydroxymethyltransferase suggests that, during photorespiration, the reaction must be permanently pushed toward the formation of serine (the unfavourable direction) to allow the recycling of tetrahydrofolate necessary for the operation of the glycine decarboxylase T-protein.
Rosemary (Rosmarinus officinalis L.) Extract as a Potential Complementary Agent in Anticancer Therapy (2015)

Cancer remains an important cause of mortality nowadays and, therefore, new therapeutic approaches are still needed. Rosemary (Rosmarinus officinalis L.) has been reported to possess antitumor activities both in vitro and in animal studies. Some of these activities were attributed to its major components, such as carnosic acid, carnosol, ursolic acid, and rosmarinic acid. Initially, the antitumor effects of rosemary were attributed to its antioxidant activity. However, in recent years, a lack of correlation between antioxidant and antitumor effects exerted by rosemary was reported, and different molecular mechanisms were related to its tumor inhibitory properties. Moreover, supported by the U.S. Food and Drug Administration and the European Food and Safety Authority, specific compositions of rosemary extract were demonstrated to be safe for human health and used as antioxidant additive in foods, suggesting the potential easy application of this agent as a complementary approach in cancer therapy. In this review, we aim to summarize the reported anticancer effects of rosemary, the demonstrated molecular mechanisms related to these effects and the interactions between rosemary and currently used anticancer agents. The possibility of using rosemary extract as a complementary agent in cancer therapy in comparison with its isolated components is discussed.
Yeast expression of a catalytic antibody with chorismate mutase activity (1991)

The catalytic antibody 1F7 promotes the rearrangement of chorismate into prephenate. We cloned and sequenced the genes encoding this catalyst to determine the origin of the observed rates and specificity. The antibody cDNAs were modified and inserted into inducible expression vectors. Simultaneous intracellular expression of the light and truncated heavy chains in strains of the yeast Saccharomyces cerevisiae lacking natural chorismate mutase resulted in the production of properly folded and assembled Fab antibody. Assembly of the light and heavy immunoglobulin chains is roughly 60-70% efficient in our in vivo system, lagging behind light chain synthesis throughout log and stationary phase. Nevertheless, high intracellular levels of functional Fab antibody (0.1% of total cellular protein) were obtained with an ultra-high copy number plasmid. As yeast-derived 1F7(Fab) catalyzes the chorismate mutase reaction with the same specific activity as antibody isolated from the hybridoma, our expression system now makes possible the application of classical and "reverse" genetics to the study and improvement of this first-generation abzyme.
Nanoscale distribution of mitochondrial import receptor Tom20 is adjusted to cellular conditions and exhibits an inner-cellular gradient (2011)

The translocase of the mitochondrial outer membrane (TOM) complex is the main import pore for nuclear-encoded proteins into mitochondria, yet little is known about its spatial distribution within the outer membrane. Super-resolution stimulated emission depletion microscopy was used to determine quantitatively the nanoscale distribution of Tom20, a subunit of the TOM complex, in more than 1,000 cells. We demonstrate that Tom20 is located in clusters whose nanoscale distribution is finely adjusted to the cellular growth conditions as well as to the specific position of a cell within a microcolony. The density of the clusters correlates to the mitochondrial membrane potential. The distributions of clusters of Tom20 and of Tom22 follow an inner-cellular gradient from the perinuclear to the peripheral mitochondria. We conclude that the nanoscale distribution of the TOM complex is finely adjusted to the cellular conditions, resulting in distribution gradients both within single cells and between adjacent cells.
Soft hydrogels interpenetrating silicone—A polymer network for drug‐releasing medical devices (2015)

Materials for the next generation of medical devices will require not only the mechanical stability of current devices, but must also possess other properties such as sustained release of drugs in a controlled manner over a prolonged period of time. This work focuses on creating such a sophisticated material by forming an interpenetrating polymer network (IPN) material through modification of silicone elastomers with a poly(2-hydroxyethyl methacrylate) (PHEMA)-based hydrogel. IPN materials with a PHEMA content in the range of 13%-38% (w/w) were synthesized by using carbon dioxide-based solvent mixtures under high pressure. These IPNs were characterized with regard to microstructure as well as ability of the hydrogel to form a surface-connected hydrophilic carrier network inside the silicone. A critical limit for hydrogel connectivity was found both via simulation and by visualization of water uptake in approximately 25% (w/w) PHEMA, indicating that entrapment of gel occurs at low gel concentrations. The optimized IPN material was loaded with the antibiotic ciprofloxacin, and the resulting drug release was shown to inhibit bacterial growth when placed on agar, thus demonstrating the potential of this IPN material for future applications in drug-releasing medical devices.
Two Cases of Ruminococcus gnavus Bacteremia Associated with Diverticulitis (2013)

We report two cases of bacteremia with the anaerobic bacterium Ruminococcus gnavus. In both cases, the bacteremia was associated with diverticular disease. Preliminary conventional identification suggested peptostreptococci, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis did not produce scores high enough for species identification. Finally, the bacteria were identified by 16S rRNA gene sequencing.
IL-15 Induces the Expression of Chemokines and Their Receptors in T Lymphocytes (1999)

IL-15 is a T cell growth factor that shares many biological activities with IL-2 and uses the same beta/gamma polypeptides of the IL-2R complex for signal transduction. Accumulating evidence implicates an important role for this cytokine in the inflammatory response of the host. Consistent with such a role, IL-15 has been shown to be a chemoattractant for T lymphocytes, NK cells, and neutrophils. Extending these observations, we now show that IL-15 is a potent inducer of CC-, CXC-, and C-type chemokines in T lymphocytes. In addition, we demonstrate that IL-15 induces CC chemokine receptors, but not CXC chemokine receptors, in a dose-dependent manner. Thus, our findings suggest that the proinflammatory effects of IL-15 at least in part may be due to the induction of chemokines and their receptors in T cells. Furthermore, we demonstrate that IL-15 promotes entry and replication of macrophage-tropic HIV in T lymphocytes and suggest a plausible mechanism by which IL-15, a cytokine that is elevated in HIV-infected individuals, may promote the transition of HIV displaying the M-tropic phenotype primarily associated with the initial transmission into the T cell-tropic phenotype that predominates as the disease progresses.
Animal Models of Bacterial Keratitis (2011)

Bacterial keratitis is a disease of the cornea characterized by pain, redness, inflammation, and opacity. Common causes of this disease are Pseudomonas aeruginosa and Staphylococcus aureus. Animal models of keratitis have been used to elucidate both the bacterial factors and the host inflammatory response involved in the disease. Reviewed herein are animal models of bacterial keratitis and some of the key findings in the last several decades.
Facial Expression Biometrics Using Statistical Shape Models (2009)

This paper describes a novel method for representing different facial expressions based on the shape space vector (SSV) of the statistical shape model (SSM) built from 3D facial data. The method relies only on the 3D shape, with texture information not being used in any part of the algorithm, that makes it inherently invariant to changes in the background, illumination, and to some extent viewing angle variations. To evaluate the proposed method, two comprehensive 3D facial data sets have been used for the testing. The experimental results show that the SSV not only controls the shape variations but also captures the expressive characteristic of the faces and can be used as a significant feature for facial expression recognition. Finally the paper suggests improvements of the SSV discriminatory characteristics by using 3D facial sequences rather than 3D stills.
MODTRAN 5: a reformulated atmospheric band model with auxiliary species and practical multiple scattering options: update (2005)

The MODTRAN<sup>TM</sup>5 radiation transport (RT) model is a major advancement over earlier versions of the MODTRAN<sup>TM</sup> atmospheric transmittance and radiance model. New model features include (1) finer spectral resolution via the Spectrally Enhanced Resolution MODTRAN (SERTRAN) molecular band model, (2) a fully coupled treatment of auxiliary molecular species, and (3) a rapid, high fidelity multiple scattering (MS) option. The finer spectral resolution improves model accuracy especially in the mid- and long-wave infrared atmospheric windows; the auxiliary species option permits the addition of any or all of the suite of HITRAN molecular line species, along with default and user-defined profile specification; and the MS option makes feasible the calculation of Vis-NIR databases that include high-fidelity scattered radiances.
Mutant studies of phosphofructo-2-kinases do not reveal an essential role of fructose-2, 6-bisphosphate in the regulation of carbon fluxes in yeast cells (1997)

The effect of the allosteric regulator fructose-2,6-bisphosphate (F2,6bP) on the regulation of carbohydrate metabolism was investigated in vivo with Saccharomyces cerevisiae mutants containing no, very high or unregulated 6-phosphofructo-2-kinase activity. Simultaneous overproduction of F2,6bP and 6-phosphofructo-1-kinase activity did not increase the glycolytic flux to ethanol. Overexpression of fructose-1,6-bisphosphatase during growth on glucose in a mutant strain devoid of F2,6bP did not cause pronounced effects on the cells. Moreover, high levels of F2,6bP during growth on ethanol in a strain with a highly active 6-phosphofructo-2-kinase enzyme did not affect either carbon flux to glycogen or growth rate. Site-directed mutagenesis of 6-phosphofructo-2-kinase (Pfk26) revealed that serine 644 is involved in the activation of Pfk26 by protein kinase A phosphorylation, but that, additionally, the enzyme can be further activated by phosphorylation of another amino acid residue. The results demonstrate that F2,6bP is not needed to sustain an adequate glycolytic flux under fermentative conditions, but rather is concerned with the homeostasis of metabolite concentrations. Moreover, they fail to indicate a physiological significance for inhibition of fructose-1,6-bisphosphatase by F2,6bP.
Trimerization of the heat shock transcription factor by a triple-stranded .alpha.-helical coiled-coil (1992)

We have isolated and characterized a 91 amino acid fragment of the heat shock transcription factor from both Saccharomyces cerevisiae and Kluyveromyces lactis. The two protein fragments behave similarly: they form homotrimers, as indicated by sedimentation equilibrium and cross-linking, and contain approximately 80% alpha-helix, as indicated by circular dichroism. Sedimentation velocity and diffusion coefficients indicate that they have an elongated, nonspherical shape. We conclude the following: these fragments contain a domain which forms a trimer via a triple-stranded alpha-helical coiled-coil, similar to that found in influenza hemagglutinin.
Determination of Oligosaccharides in Pompe Disease by Electrospray Ionization Tandem Mass Spectrometry (2002)

Measurements of oligosaccharide concentrations in urine by this new method have potential application for the diagnosis and monitoring of patients with Pompe disease. Plasma analysis may have limited application for infantile patients, but analysis of blood spots does not discriminate between controls and affected individuals.
Sensing Trending Topics in Twitter (2013)

Online social and news media generate rich and timely information about real-world events of all kinds. However, the huge amount of data available, along with the breadth of the user base, requires a substantial effort of information filtering to successfully drill down to relevant topics and events. Trending topic detection is therefore a fundamental building block to monitor and summarize information originating from social sources. There are a wide variety of methods and variables and they greatly affect the quality of results. We compare six topic detection methods on three Twitter datasets related to major events, which differ in their time scale and topic churn rate. We observe how the nature of the event considered, the volume of activity over time, the sampling procedure and the pre-processing of the data all greatly affect the quality of detected topics, which also depends on the type of detection method used. We find that standard natural language processing techniques can perform well for social streams on very focused topics, but novel techniques designed to mine the temporal distribution of concepts are needed to handle more heterogeneous streams containing multiple stories evolving in parallel. One of the novel topic detection methods we propose, based on -grams cooccurrence and topic ranking, consistently achieves the best performance across all these conditions, thus being more reliable than other state-of-the-art techniques.
NMR techniques for characterization of ligand binding: Utility for lead generation and optimization in drug discovery (1999)

Over the last ten years, nmr spectroscopy has evolved into an important discipline in drug discovery. Initially, nmr was most useful as a technique to provide structural information regarding protein drug targets and target-ligand interactions. More recently, it has been shown that nmr may be used as an alternative method for identification of small molecule ligands that bind to protein drug targets. High throughput implementation of these experiments to screen small molecule libraries may lead to identification of potent and novel lead compounds. In this review, we will use examples from our own research to illustrate how nmr experiments to characterize ligand binding may be used to both screen for novel compounds during the process of lead generation, as well as provide structural information useful for lead optimization during the latter stages of a discovery program.