gebhart/patrepeval huggingface dataset:
Interaction of Human Pancreatic Ribonuclease with Human Ribonuclease Inhibitor (2001)

Mammalian ribonucleases interact very strongly with the intracellular ribonuclease inhibitor (RI). Eukaryotic cells exposed to mammalian ribonucleases are protected from their cytotoxic action by the intracellular inhibition of ribonucleases by RI. Human pancreatic ribonuclease (HPR) is structurally and functionally very similar to bovine RNase A and interacts with human RI with a high affinity. In the current study, we have investigated the involvement of Lys-7, Gln-11, Asn-71, Asn-88, Gly-89, Ser-90, and Glu-111 in HPR in its interaction with human ribonuclease inhibitor. These contact residues were mutated either individually or in combination to generate mutants K7A, Q11A, N71A, E111A, N88R, G89R, S90R, K7A/E111A, Q11A/E111A, N71A/E111A, K7A/N71A/E111A, Q11A/N71A/E111A, and K7A/Q11A/N71A/E111A. Out of these, eight mutants, K7A, Q11A, N71A, S90R, E111A, Q11A/E111A, N71A/E111A, and K7A/N71A/E111A, showed an ability to evade RI more than the wild type HPR, with the triple mutant K7A/N71A/E111A having the maximum RI resistance. As a result, these variants exhibited higher cytotoxic activity than wild type HPR. The mutation of Gly-89 in HPR produced no change in the sensitivity of HPR for RI, whereas it has been reported that mutating the equivalent residue Gly-88 in RNase A yielded a variant with increased RI resistance and cytotoxicity. Hence, despite its considerable homology with RNase A, HPR shows differences in its interaction with RI. We demonstrate that interaction between human pancreatic ribonuclease and RI can be disrupted by mutating residues that are involved in HPR-RI binding. The inhibitor-resistant cytotoxic HPR mutants should be useful in developing therapeutic molecules.
NMR Solution Structure of a Complex of Calmodulin with a Binding Peptide of the Ca2+ Pump, (1999)

The three-dimensional structure of the complex between calmodulin (CaM) and a peptide corresponding to the N-terminal portion of the CaM-binding domain of the plasma membrane calcium pump, the peptide C20W, has been solved by heteronuclear three-dimensional nuclear magnetic resonance (NMR) spectroscopy. The structure calculation is based on a total of 1808 intramolecular NOEs and 49 intermolecular NOEs between the peptide C20W and calmodulin from heteronuclear-filtered NOESY spectra and a half-filtered experiment, respectively. Chemical shift differences between free Ca(2+)-saturated CaM and its complex with C20W as well as the structure calculation reveal that C20W binds solely to the C-terminal half of CaM. In addition, comparison of the methyl resonances of the nine assigned methionine residues of free Ca(2+)-saturated CaM with those of the CaM/C20W complex revealed a significant difference between the N-terminal and the C-terminal domain; i.e., resonances in the N-terminal domain of the complex were much more similar to those reported for free CaM in contrast to those in the C-terminal half which were significantly different not only from the resonances of free CaM but also from those reported for the CaM/M13 complex. As a consequence, the global structure of the CaM/C20W complex is unusual, i.e., different from other peptide calmodulin complexes, since we find no indication for a collapsed structure. The fine modulation in the peptide protein interface shows a number of differences to the CaM/M13 complex studied by Ikura et al. [Ikura, M., Clore, G. M., Gronenborn, A. M., Zhu, G., Klee, C. B., and Bax, A. (1992) Science 256, 632-638]. The unusual binding mode to only the C-terminal half of CaM is in agreement with the biochemical observation that the calcium pump can be activated by the C-terminal half of CaM alone [Guerini, D., Krebs, J., and Carafoli, E. (1984) J. Biol. Chem. 259, 15172-15177].
TabBO: a model reflecting common molecular features of androgen-independent prostate cancer. (2000)

We established two human prostate cancer cell lines, MDA PCa 2a and MDA PCa 2b, the TabBO model system, that reflect common features of human androgen-independent prostate cancer that are not present in other model systems: bone origin, prostate-specific antigen production, androgen receptor expression, and androgen sensitivity. We therefore hypothesized that molecular pathways in our model system reflect common alterations responsible for the progression of a subset of human prostate cancer. Progression to androgen independence has been hypothesized to be largely associated with impairment of the regulation of cell growth or apoptosis of prostate cancer cells. Therefore, in this study, we examined molecular markers known or suspected to be important in prostate cancer progression and key regulators of cell growth and apoptosis: p53, p21WAF1/CIP1, Bcl-2, Bax, retinoblastoma (Rb), and p16INK4A/MITS1. We analyzed the expression of these markers in the cell lines, their tumor of origin, and tumors derived from the cell lines by s.c. inoculation into nude mice. DNA sequencing of the entire open reading frames of the p53 and p21 genes revealed no mutations. Additionally, accumulation of the p53 protein was not found by Western blot analysis, nor was overexpression of the Bcl-2 oncoprotein detected. Bax expression was detected in MDA PCa 2a cells, whereas it was absent in MDA PCa 2b. Rb and p16 protein expression was normal as measured by both Western blot and immunochemical analyses. Immunohistochemical studies of p53, p21, Bcl-2, and Rb in both samples from the original human cancer from which the lines were derived and mouse xenografts derived from the lines revealed similar levels of protein. These results are consistent with reports indicating that 40-50% of bone metastases of prostate cancer have wild-type p53, 50-70% do not overexpress the Bcl-2 protein, and mutations in the p21 gene are rare. Therefore, we conclude that MDA PCa 2a and MDA PCa 2b reflect molecular pathways in a common subset of human androgen-independent prostate cancer and that important molecular players in apoptosis (namely, p53 and Bcl-2) seem to be intact in this subset of androgen-independent prostate cancer. Understanding the signal-transduction pathways operating in these cell lines may help to identify therapeutic targets for prostate cancer.
A Review of the Evidence for the Efficacy and Safety of Trazodone in Insomnia (2005)

Given the relative absence of efficacy data in patients with insomnia and the adverse events associated with trazodone's use in general, it is uncertain whether the risk/benefit ratio warrants trazodone's use in nondepressed patients with insomnia.
Bypass of carrier-induced epitope-specific suppression using a T-helper epitope. (1992)

A gonadotropin-releasing hormone (GnRH)-based vaccine is being developed as a method for non-surgical immunotherapy as immunization with this vaccine results in atrophy of the prostate. This vaccine, a conjugate of GnRH and diphtheria toxoid (DT), provides a unique hapten-carrier system for investigating the influence of carrier presensitization on antibody responses to self haptens. In a recent communication we showed that preimmunization with carriers diphtheria toxoid and tetanus toxoid results in a strain-dependent inhibition of anti-GnRH responses in mice and that T cells from carrier-presensitized mice are responsible for anti-haptenic suppression. In the present report we describe a strategy for bypassing DT-induced epitopic suppression using a T-helper epitope from DT.
Immunosuppressive effects of human CTLA4Ig in a non-human primate model of allogeneic pancreatic islet transplantation (1997)

Ag-specific T cell activation requires a CD28-mediated costimulatory interaction. This observation has suggested novel approaches to suppress donor-specific immunity, including the use of soluble CD28 antagonists, such as CTLA4Ig, which suppresses transplant rejection in small animal models. In this study, CTLA4Ig therapy was examined in a non-human primate model of allogeneic pancreatic islet transplantation. Two of five CTLA4Ig-treated monkeys showed prolonged graft survival, which correlated with donor-specific hyporesponsiveness in vitro. Humoral responses to the transplanted tissue were suppressed in all treated animals. These results suggest that CTLA4Ig is effective in suppressing both humoral and cellular immune responses in a non-human primate model of allogeneic transplantation.
Cationic Ring-Opening Polymerization of 1,3-Benzoxazines: Mechanistic Study Using Model Compounds (2010)

The benzoxazine monomer is used to simplify the study of the benzoxazine initiation mechanism. The HPLC retention time and the 1H NMR spectra of crude products from the benzoxazine reaction are compared with the results from a vast number of pure model compounds, which are synthesized based on the hypothesized mechanisms. Products involved in the process are identified, with species having benzoxazine structures, Mannich base and other components (acetal, nonacetal phenoxy structures, and methylene bridge structure). Initiation mechanisms of benzoxazine, e.g., the oxygen protonation and the nitrogen protonation, are proposed.
Estimation of the Maximum Tire-Road Friction Coefficient (2003)

We develop and test a “slip-based” method to estimate the maximum available tire-road friction during braking. The method is based on the hypothesis that the low-slip, low-μ parts of the slip curve used during normal driving can indicate the maximum tire-road friction coefficient, μmax. We find support for this hypothesis in the literature and through experiments. The friction estimation algorithm uses data from short braking maneuvers with peak accelerations of 3.9 m/s2 to classify the road surface as either dry μmax≈1 or lubricated μmax≈0.6. Significant measurement noise makes it difficult to detect the subtle effect being measured, leading to a misclassification rate of 20%.
Ensuring Trustworthy Spectrum Sensing in Cognitive Radio Networks (2006)

Cognitive Radio (CR) is a promising technology that can alleviate the spectrum shortage problem by enabling unlicensed users equipped with CRs to coexist with incumbent users in licensed spectrum bands without inducing interference to incumbent communications. Spectrum sensing is one of the essential mechanisms of CRs that has attracted great attention from researhers recently. Although the operational aspects of spectrum sensing are being investigated actively, its security aspects have garnered little attention. In this paper, we describe an attack that poses a great threat to spectrum sensing. In this attack, which is called the primary user emulation (PUE) attack, an adversary's CR transmits signals whose characteristics emulate those of incumbent signals. The highly flexible, software-based air interface of CRs makes such an attack possible. Our investigation shows that a PUE attack can severely interfere with the spectrum sensing process and significantly reduce the channel resources available to legitimate unlicensed users. As a way of countering this threat, we propose a transmitter verification procedure that can be integrated into the spectrum sensing mechanism. The transmitter verification procedure employs a location verification scheme to distinguish incumbent signals from unlicensed signals masquerading as incumbent signals. Two alternative techniques are proposed to realize location verification: Distance Ratio Test and Distance Difference Test. We provide simulation results of the two techniques as well as analyses of their security in the paper.
Randomized Trial of Labor Induction in Women 35 Years of Age or Older (2016)

Among women of advanced maternal age, induction of labor at 39 weeks of gestation, as compared with expectant management, had no significant effect on the rate of cesarean section and no adverse short-term effects on maternal or neonatal outcomes. (Funded by the Research for Patient Benefit Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN11517275.).
Experimental Results on Electrorheology of Liquid Crystalline Polymer Solutions (2008)

The electrorheological (ER) effect is known as the enhancement of the apparent viscosity upon application of an external electric field. Suspensions of polarizable particles in non‐conducting solvents are the most studied electrorheological fluids, however, liquid crystalline materials may also present ER effect as long as their dielectric anisotropy is positive. In the liquid crystalline state of a positive dielectric anisotropy, the application of the electric field makes the director align perpendicular to the flow direction, thus increasing the apparent viscosity. In this work results of two liquid crystalline polymer solutions, acetoxypropylcellulose (APC) in dimethylacetamide (DMAc) and poly‐γ‐benzyl‐L‐glutamate (PBLG) in 1,4‐dioxane, presenting opposite behavior upon application of the electric field, will be presented. APC/DMAc (negative dielectric anisotropy) presents a decrease of the apparent viscosity upon application of the electric field, as expected, while PBLG/1,4‐dioxane (positive dielectric anisotropy) presents the opposite behavior. For this last solution we will present the shear flow curves for different electric fields in function of polymer molecular weight and solution concentration.
The resistance of certain tissues to invasion. III. Cartilage extracts inhibit the growth of fibroblasts and endothelial cells in culture. (1975)

Extracts of bovine dermis and cartilage inhibit the growth of bovine endothelial cells more than that of most of the fibroblast types tested. Extracts of cartilage, a tissue rather resistant to invasion, inhibit the growth of endothelial cells more than extracts of dermis do. Since such extracts contain antiproteolytic activity, it is suggested that the inhibition of cell growth they induce is effected by protease inhibitors native to connective tissues.
In VivoBiodistribution and Clearance Studies Using Multimodal Organically Modified Silica Nanoparticles (2010)

Successful translation of the use of nanoparticles from laboratories to clinics requires exhaustive and elaborate studies involving the biodistribution, clearance, and biocompatibility of nanoparticles for in vivo biomedical applications. We report here the use of multimodal organically modified silica (ORMOSIL) nanoparticles for in vivo bioimaging, biodistribution, clearance, and toxicity studies. We have synthesized ORMOSIL nanoparticles with diameters of 20-25 nm, conjugated with near-infrared (NIR) fluorophores and radiolabeled them with (124)I, for optical and PET imaging in vivo. The biodistribution of the nontargeted nanoparticles was studied in nontumored nude mice by optical fluorescence imaging, as well by measuring the radioactivity from harvested organs. Biodistribution studies showed a greater accumulation of nanoparticles in liver, spleen, and stomach than in kidney, heart, and lungs. The clearance studies carried out over a period of 15 days indicated hepatobiliary excretion of the nanoparticles. Selected tissues were analyzed for any potential toxicity by histological analysis, which confirmed the absence of any adverse effect or any other abnormalities in the tissues. The results demonstrate that these multimodal nanoparticles have potentially ideal attributes for use as biocompatible probes for in vivo imaging.
Fluorescence In Situ Hybridization in Cancer and Radiation Biology (1994)

This review describes molecular cytogenetic approaches to genetic analysis including fluorescence in situ hybridization, primed in situ labeling and comparative genomic hybridization. It also summarizes the applications of this technology to physical mapping, cancer diagnosis and prognostication and in radiation biology.
Topiramate Selectively Decreases Intracortical Excitability in Human Motor Cortex (2002)

We conclude that a single dose of TPM selectively increases ICI by GABAAergic and/or glutamatergic mechanisms without a relevant influence on measures, depending on ion-channel blockade or GABAB-receptor activity. The decrease of intracortical excitability (as measured by ICI and ICF) caused by TPM may correlate with its lack of proconvulsive potential in idiopathic generalized epilepsy, because drugs without this action or with less pronounced action may exacerbate seizures in this condition.
Mapping the human membrane proteome: a majority of the human membrane proteins can be classified according to function and evolutionary origin (2009)

Abstract Background Membrane proteins form key nodes in mediating the cell's interaction with the surroundings, which is one of the main reasons why the majority of drug targets are membrane proteins. Results Here we mined the human proteome and identified the membrane proteome subset using three prediction tools for alpha-helices: Phobius, TMHMM, and SOSUI. This dataset was reduced to a non-redundant set by aligning it to the human genome and then clustered with our own interactive implementation of the ISODATA algorithm. The genes were classified and each protein group was manually curated, virtually evaluating each sequence of the clusters, applying systematic comparisons with a range of databases and other resources. We identified 6,718 human membrane proteins and classified the majority of them into 234 families of which 151 belong to the three major functional groups: receptors (63 groups, 1,352 members), transporters (89 groups, 817 members) or enzymes (7 groups, 533 members). Also, 74 miscellaneous groups with 697 members were determined. Interestingly, we find that 41% of the membrane proteins are singlets with no apparent affiliation or identity to any human protein family. Our results identify major differences between the human membrane proteome and the ones in unicellular organisms and we also show a strong bias towards certain membrane topologies for different functional classes: 77% of all transporters have more than six helices while 60% of proteins with an enzymatic function and 88% receptors, that are not GPCRs, have only one single membrane spanning α-helix. Further, we have identified and characterized new gene families and novel members of existing families. Conclusion Here we present the most detailed roadmap of gene numbers and families to our knowledge, which is an important step towards an overall classification of the entire human proteome. We estimate that 27% of the total human proteome are alpha-helical transmembrane proteins and provide an extended classification together with in-depth investigations of the membrane proteome's functional, structural, and evolutionary features.
DNA binds and activates complement via residues 14-26 of the human C1q A chain. (1992)

The mechanism by which DNA activates the classical complement pathway was investigated, with emphasis upon the C1q binding sites involved. DNA bound to both the collagen-like and globular regions of C1q. Binding reactivity with DNA was retained after reduction/alkylation and sodium dodecyl sulfate treatment of C1q. DNA bound preferentially to the A chain of C1q. Binding sites for DNA were localized by using synthetic C1q A chain peptides to two cationic regions within residues 14-26 and 76-92, respectively. Peptides 14-26 and 76-92 avidly bound DNA in enzyme-linked immunosorbent and gel shift assays. Peptide 14-26 also precipitated with DNA and blocked its ability to bind C1q and activate C. Replacement of the two prolines with alanines or scrambling the order of the amino acids resulted in loss of ability of peptide 14-26 to inhibit C1q binding and complement activation by DNA; similar investigations showed a sequence specificity for peptide 76-92 as well. These experiments identify C1q A chain residues 14-26 as the major site, and residues 76-92 as a secondary site, through which DNA binds C1q and activates the classical complement pathway, and demonstrate that a peptide identical to residues 14-26 can modulate C1q binding and complement activation by DNA.
Cross-Linked DNA: Site-Selective “Click” Ligation in Duplexes with Bis-Azides and Stability Changes Caused by Internal Cross-Links (2012)

Heterodimeric interstrand cross-linked DNA was constructed by the "bis-click" reaction carried out on preformed oligonucleotide duplexes with the bis-azide 1. For this, alkynylated 8-aza-7-deazapurine or corresponding 5-substituted pyrimidine nucleosides were synthesized. Cross-linking resulted in chemoselective formation of heterodimeric duplexes while homodimers were suppressed. For product identification, heterodimeric DNA was prepared by the "stepwise click" reaction, while noncomplementary homodimers were accessible by "bis-click" chemistry, unequivocally. Studies on duplex melting of complementary cross-linked duplexes (heterodimers) revealed significantly increased Tm values compared to the non-cross-linked congeners. The stability of this cross-linked DNA depends on the linker length and the site of modification. Cross-linked homodimers hybridized with single-stranded complementary oligonucleotides show much lower stability.
Geometric Control of Cell Life and Death (1997)

Human and bovine capillary endothelial cells were switched from growth to apoptosis by using micropatterned substrates that contained extracellular matrix-coated adhesive islands of decreasing size to progressively restrict cell extension. Cell spreading also was varied while maintaining the total cell-matrix contact area constant by changing the spacing between multiple focal adhesion-sized islands. Cell shape was found to govern whether individual cells grow or die, regardless of the type of matrix protein or antibody to integrin used to mediate adhesion. Local geometric control of cell growth and viability may therefore represent a fundamental mechanism for developmental regulation within the tissue microenvironment.
Principal modes in multimode waveguides (2005)

We generalize the concept of principal states of polarization and prove the existence of principal modes in multimode waveguides. Principal modes do not suffer from modal dispersion to first order of frequency variation and form orthogonal bases at both the input and the output ends of the waveguide. We show that principal modes are generally different from eigenmodes, even in uniform waveguides, unlike the special case of a single-mode fiber with uniform birefringence. The difference is most pronounced when different eigenmodes possess similar group velocities and when their field patterns vary as a function of frequency. This work may provide a new basis for analysis and control of dispersion in multimode fiber systems.
Efficiency of hot-carrier solar energy converters (1982)

A single-threshold quantum-utilizing device in which the excited carriers thermally equilibrate among themselves, but not with the environment, can convert solar energy with an efficiency approaching that of an infinite-threshold device. Such a hot-carrier flat-plate device operated under typical terrestrial conditions (AM 1.5 illumination, 300 K) can convert solar energy with an efficiency of 66%, substantially exceeding the 33% maximum efficiency of a quantum device operating at thermal equilibrium, and the 52% maximum efficiency of an ideal thermal conversion device. This high efficiency is achieved in part through an unusual inversion, in which the chemical potential of the excited electronic band is below that of the ground band. This negative potential difference reduces radiation losses, permitting a low threshold energy, and a high Carnot efficiency resulting from a high carrier temperature.