gebhart/patrepeval huggingface dataset:
Inhibition of nuclear translocation of nuclear factor-{kappa}B contributes to 3,3'-diindolylmethane-induced apoptosis in breast cancer cells. (2005)

Dietary indole-3-carbinol (I3C), a natural compound present in vegetables of the genus Brassica, showed clinical benefits and caused apoptosis in breast cancer cells. Our laboratory and others have shown that I3C induces apoptosis in breast cancer cells mediated by inactivation of Akt and nuclear factor-kappaB (NF-kappaB) pathway. 3,3'-Diindolylmethane (DIM), a major in vivo acid-catalyzed condensation product of I3C, also showed some benefit in breast cancer. However, the precise molecular mechanism(s) by which DIM induces apoptosis in breast cancer cells has not been fully elucidated. Hence, we investigated whether DIM-induced apoptosis of breast cancer cells could also be mediated by inactivation of Akt and NF-kappaB. We found that DIM induces apoptotic processes in MCF10A derived malignant (MCF10CA1a) cell lines but not in nontumorigenic parental MCF10A cells. DIM specifically inhibits Akt kinase activity and abrogates the epidermal growth factor-induced activation of Akt in breast cancer cells, similar to those observed for I3C. We also found that DIM reduces phosphorylation of IkappaBalpha, an inhibitor of NF-kappaB. Our confocal microscopy study clearly showed that DIM blocks the translocation of p65, a subunit of NF-kappaB to the nucleus. DNA binding analysis and transfection studies with IkappaB kinase cDNA revealed that overexpression of IkappaB kinase mediates IkappaBalpha phosphorylation, which activates NF-kappaB, and this activation was completely abrogated by DIM treatment. Taken together, these results showed for the first time that the inactivation of Akt and NF-kappaB activity also plays important roles in DIM-induced apoptosis in breast cancer cells, which seems to be more relevant to in vivo situations.
Contribution of Growth Hormone to the Adipogenic Activity of Serum* (1984)

GH promotes the conversion of cultured preadipose 3T3 cells into adipose cells. The serum of most animals also promotes this differentiation. In order to determine the extent to which GH is responsible for the adipogenic activity of serum, we used a specific antiserum able to suppress completely the adipogenic activity of rat and bovine GH. This antiserum also suppressed all the adipogenic activity secreted into culture medium by a rat pituitary cell line as well as all the adipogenic activity of crude bovine pituitary extract. When tested against the adipogenic activity of serum, the antiserum to GH reduced the activity by one third to half. It is concluded that 1) GH in the concentration and form present in serum is an effective promoter of adipose differentiation, and 2) there exists in serum another adipogenic activity not immunochemically recognizable as GH. This activity is presumed to be of nonpituitary origin.
Acyl-coenzyme A (1999)

In addition to acyl-coenzyme A:cholesterol acyltransferase-1 (ACAT1), an enzyme in the endoplasmic reticulum of cells found ubiquitously throughout the body, data recently obtained in at least three mammalian species, including nonhuman primates, mice and humans, demonstrate the presence of an additional ACAT (EC 2.1.3.26), termed ACAT2, which is localized to the endoplasmic reticulum of liver and intestine. Data suggest that ACAT2 may be the enzyme responsible for cholesteryl ester secretion into apolipoprotein B-containing lipoproteins. We have hypothesized that oversecretion of cholesteryl esters produced by the action of hepatic ACAT2 could account for the increased atherogenicity associated with cholesteryl ester-enriched LDL in nonhuman primates. In such cases, ACAT2 is an appealing target for therapy to reduce coronary heart disease.
Talin is phosphorylated on tyrosine in chicken embryo fibroblasts transformed by Rous sarcoma virus. (1986)

We have examined the extent of tyrosine phosphorylation of talin, a component of the cytoskeleton localized in the focal adhesions and, therefore, a potential substrate of p60v-src, the transforming protein of Rous sarcoma virus. p60v-src is a tyrosine kinase that induces high levels of phosphotyrosine and the disorganization of the cytoskeleton in transformed cells. With a polyclonal antibody utilized in a previous study [Maher, P. A., Pasquale, E. B., Wang, J. Y. J. & Singer, S. J. (1985) Proc. Natl. Acad. Sci. USA 82, 6576-6580] for the detection of tyrosine-phosphorylated proteins, we have detected phosphotyrosine residues in talin molecules immunoprecipitated from Rous sarcoma virus-transformed, but not normal, chicken embryo fibroblasts. Phospho amino acid analysis of talin from the infected cells confirmed the presence of phosphotyrosine, in addition to phosphoserine and phosphothreonine. The extent of tyrosine modification in talin was compared to that in vinculin, the other focal adhesion component previously found to contain enhanced levels of phosphotyrosine in various retrovirus-transformed cells. A considerably (3 times) larger fraction of the talin than of the vinculin molecules was found to be phosphorylated on tyrosine. The phosphorylation of talin on tyrosine may be crucial for the expression of the abnormal morphology characteristic of cells transformed by Rous sarcoma virus.
Effect of Salt Concentration on the Conductivity of PEO-Based Composite Polymeric Electrolytes (1998)

The effect of salt concentration on the molal conductivity of various composite electrolytes was studied. Conductivity enhancement is achieved for composite electrolytes over the basic poly(ethylene oxide)−LiClO4 system in the salt concentration range where the filler concentration corresponds to that of LiClO4. On the basis of impedance spectroscopy, DSC, and FT-IR studies, it is concluded that changes in the conductivity result from acid−base type interactions involving polyether oxygens, filler acid or base centers, and alkali metal cations. The effect of a filler is to change the fraction of available oxygen sites which in turn results in changes in the formation of ionic aggregates. The region in which the enhancement of ionic conductivity is observed corresponds to a decrease in the fraction of contact-ion pairs and higher aggregates; this is due to the location of filler molecules in the vicinity of the coordination sphere of Li+ cations.
Fault-tolerant quantum computation against biased noise (2008)

We formulate a scheme for fault-tolerant quantum computation that works effectively against highly biased noise, where dephasing is far stronger than all other types of noise. In our scheme, the fundamental operations performed by the quantum computer are single-qubit preparations, single-qubit measurements, and conditional-phase (CPHASE) gates, where the noise in the CPHASE gates is biased. We show that the accuracy threshold for quantum computation can be improved by exploiting this noise asymmetry; e.g., if dephasing dominates all other types of noise in the CPHASE gates by four orders of magnitude, we find a rigorous lower bound on the accuracy threshold higher by a factor of 5 than for the case of unbiased noise.
Anion binding in covalent and self-assembled molecular capsules (2010)

This critical review describes selected examples extracted from the extensive literature generated during the past 42 years on the topic of anion binding in molecular capsules. The goal of including anions in molecular capsules emerges from the idea of incorporating the traits exhibited by biological receptors into synthetic ones. At the outset of this research area the capsules were unimolecular. The scaffold of the receptor was designed to covalently link a series of functional groups that could converge into a cavity and to avoid its collapse. The initial examples involved the encapsulation of one monoatomic spherical anion. With time, the cavity size of the receptor was increased and encapsulation of polyatomic anions and co-encapsulation became a reality. Synthetic economy fueled the use of aggregates of self-complementary molecules rather than one large molecule as capsules. The main purpose of this review is to give a general overview of the topic which might be of interest to supramolecular or non supramolecular chemists alike (149 references).
Adenovirus-Based Genetic Vaccines for Biodefense (2005)

The robust host responses elicited against transgenes encoded by (E1-)(E3-) adenovirus (Ad) gene transfer vectors can be used to develop Ad-based vectors as platform technologies for vaccines against potential bioterror pathogens. This review focuses on pathogens of major concern as bioterror agents and why Ad vectors are ideal as anti-bioterror vaccine platforms, providing examples from our laboratories of using Ad vectors as vaccines against potential bioterror pathogens and how Ad vectors can be developed to enhance vaccine efficacy in the bioterror war.
Review of Fructosyl Amino Acid Oxidase Engineering Research: A Glimpse into the Future of Hemoglobin A1c Biosensing (2009)

Glycated proteins, particularly glycated hemoglobin A1c, are important markers for assessing the effectiveness of diabetes treatment. Convenient and reproducible assay systems based on the enzyme fructosyl amino acid oxidase (FAOD) have become attractive alternatives to conventional detection methods. We review the available FAOD-based assays for measurement of glycated proteins as well as the recent advances and future direction of FAOD research. Future research is expected to lead to the next generation of convenient, simple, and economical sensors for glycated protein, ideally suited for point-of-care treatment and self-monitoring applications.
First-Person Shooter Controls on Touchscreen Devices: a Heuristic Evaluation of Three Games on the iPod Touch (2013)

Today's touchscreen devices have a large amount of computing power which enables them to run high performance software, such as first-person shooter games rendered in 3D. Devices such as the iPod Touch that were originally built for music and other media consumption also provide a wide variety of features. For example, the iPod Touch can be used to surf the Internet, play quality video and audio and run complex video games.\n\nThis thesis concentrates on first-person shooters games on the iPod Touch and provides a detailed breakdown of how developers have used the device's touch interface in their games. Related research, especially regarding first-person shooters and touch input, is explored and discussed. Completely new heuristics were developed in order to analyze the properties and effectiveness of the controls.\n\nIn total, three iPod Touch games and nine control modes were evaluated. The results showed that the effectiveness of the controls was lacking. Target acquisition and tracking proved to be especially problematic. The results followed conclusions and observations made in related research. Suggestions for future work include investigating touchscreen hardware improvements and exploring different FPS game designs for mobile platforms.\n\nAsiasanat:first-person shooter, FPS, touch input, iPhone, iPod Touch, haptic user interface, mobile user interface, mobile games, multi-touch input, tactile feedback, 3D
Mouse angiotensin-converting enzyme is a protein composed of two homologous domains (1989)

Angiotensin-converting enzyme (ACE) is a dipeptidyl carboxypeptidase that converts angiotensin I into the potent vasoconstrictor angiotensin II. We have used cDNA and genomic sequences to assemble a composite cDNA, ACE.315, encoding the entire amino acid sequence of mouse converting enzyme. ACE.315 contains 4838 base pairs and encodes a protein of 1278 amino acids (147.4 kDa) after removal of a 34-amino acid signal peptide. Within the protein, there are two large areas of homologous sequence, each containing a potential Zn-binding region and catalytic site. These homologous regions are approximately half the size of the whole ACE protein and suggest that the modern ACE gene is the duplicated product of a precursor gene. Mouse ACE is 83% homologous to human ACE in both nucleic acid and amino acid sequence, and like human ACE, contains a hydrophobic region in the carboxyl terminus that probably anchors the enzyme to the cell membrane (Soubrier, F., Alhenc-Gelas, F., Hubert, C., Allegrini, J., John, M., Tregear, G., and Corvol, P. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 9386-9390). Northern analysis of mouse kidney, lung, and testis RNA demonstrates that the testicular isozyme of ACE is encoded by a single, smaller RNA (2500 bases) than the two message sizes found in kidney or lung (4900 and 4150 bases), and that this testicular RNA hybridizes to the 3' portion of ACE.315.
Cell of origin strongly influences genetic selection in a mouse model of T-ALL (2011)

Identifying the normal cell from which a tumor originates is crucial to understanding the etiology of that cancer. However, retrospective identification of the cell of origin in cancer is challenging because of the accumulation of genetic and epigenetic changes in tumor cells. The biologic state of the cell of origin likely influences the genetic events that drive transformation. We directly tested this hypothesis by performing a Sleeping Beauty transposon mutagenesis screen in which common insertion sites were identified in tumors that were produced by mutagenesis of cells at varying time points throughout the T lineage. Mutation and gene expression data derived from these tumors were then compared with data obtained from a panel of 84 human T-cell acute lymphoblastic leukemia samples, including copy number alterations and gene expression profiles. This revealed that altering the cell of origin produces tumors that model distinct subtypes of human T-cell acute lymphoblastic leukemia, suggesting that even subtle changes in the cell of origin dramatically affect genetic selection in tumors. These findings have broad implications for the genetic analysis of human cancers as well as the production of mouse models of cancer.
Humanized monoclonal antibody armanezumab specific to N-terminus of pathological tau: characterization and therapeutic potency (2017)

These findings suggest that Armanezumab could be therapeutic in clinical studies for treatment of AD.
Human SWI-SNF Component BRG1 Represses Transcription of the c- fos Gene (1999)

Yeast and mammalian SWI-SNF complexes regulate transcription through active modification of chromatin structure. Human SW-13 adenocarcinoma cells lack BRG1 protein, a component of SWI-SNF that has a DNA-dependent ATPase activity essential for SWI-SNF function. Expression of BRG1 in SW-13 cells potentiated transcriptional activation by the glucocorticoid receptor, which is known to require SWI-SNF function. BRG1 also specifically repressed transcription from a transfected c-fos promoter and correspondingly blocked transcriptional activation of the endogenous c-fos gene. Mutation of lysine residue 798 in the DNA-dependent ATPase domain of BRG1 significantly reduced its ability to repress c-fos transcription. Repression by BRG1 required the cyclic AMP response element of the c-fos promoter but not nearby binding sites for Sp1, YY1, or TFII-I. Using human C33A cervical carcinoma cells, which lack BRG1 and also express a nonfunctional Rb protein, transcriptional repression by BRG1 was weak unless wild-type Rb was also supplied. Interestingly, Rb-dependent repression by BRG1 was found to take place through a pathway that is independent of transcription factor E2F.
LA-1 oncogene. A possible new prognostic index for evaluating cervical squamous intraepithelial lesions. (1993)

Cervical biopsies from 96 patients referred to the Union Memorial Hospital Colposcopy Clinic were analyzed for the expression of the LA-1 oncogene by using an antibody directed against a 13 amino acid epitope of the oncogene product. The expression of the oncogene was found to correlate with the grade of the cervical intraepithelial lesion. A trend was suggested even though chi 2 analysis was not significant (P = .08). Further studies are warranted to determine whether the LA-1 test predicts persistence or progression of the disease.
Surface Initiated Living Cationic Polymerization of 2-Oxazolines (1998)

A self-assembled monolayer on a planar gold substrate has been used to initiate the living cationic ring-opening polymerization of 2-ethyl-2-oxazoline. The polymer chain end was functionalized with an alkyl moiety by means of the termination reaction in order to form an amphiphilic brush-type layer. The resulting layer (d ∼ 10 nm) of linear poly(N-propionylethylenimine) (PPEI) is of uniform thickness and was found to be very stable.
Immunoconjugates comprised of drugs with impaired cellular permeability: A new approach to targeted therapy (2004)

623 A great deal of interest has surrounded the use of monoclonal antibodies (mAbs) for the selective delivery of cytotoxic agents to tumor cells. Although the approach is conceptually appealing, several limitations have been identified, including the physiological barriers to mAb extravasation and intratumoral penetration, conjugate immunogenicity, non-specific conjugate uptake, low drug potency, and inefficient release of active drug. In previous work (Doronina, et al. Nature Biotech. 7, 778-784, 2003; Francisco, et al. Blood, 102, 1458-1465, 2003), we addressed some of these issues in developing cAC10-valine-citrulline-MMAE, a cathepsin B cleavable conjugate that delivers the highly potent antimitotic agent monomethyl auristatin E (MMAE) inside CD30 positive tumor cells recognized by the chimeric mAb, cAC10. One of the advantages in using MMAE as the drug component, is that being totally synthetic, it is amenable to extensive modification. Here, we describe novel analogues of MMAE that are designed for enhanced efficacy and lower toxicity. MMAF is an acidic form of MMAE that has reduced cytotoxic activity compared to MMAE, most likely due to impaired intracellular uptake. MMAF is significantly less potent than MMAE on a diverse panel of tumor cell lines, and has a >6-fold increased MTD in mice. However, mAb-valine-citrulline-MMAF conjugates are >10 times more potent than corresponding MMAE conjugates, presumably due to intracellular drug entrapment. Further evidence that this mechanism of enhanced potency stems from the finding that mAb-valine-citrulline-MMAF conjugates are as much as 400-fold more potent on antigen positive cells than the free MMAF drug. A phenylenediamine adduct of the auristatin acid, AFP, was also found to be highly potent when linked to mAbs through the cathepsin cleavable valine-citrulline linker. Upon intracellular uptake the mAb-valine-citrulline-AFP conjugates are subject to hydrolysis of the phenylenediamine unit, leading to the release of active AF. These new conjugates, comprised of an active drug that has impaired cellular permeability, are highly active and potent. Treatment of mice with low and well-tolerated doses of these conjugates leads to cures and regressions of established carcinoma and hematologic tumor xenografts. The results illustrate how mAbs can be used to enhance the potency of relatively impermeable drugs through active intracellular delivery.
Scratch-Wound Assay (2011)

The scratch-wound assay is a simple, reproducible assay commonly used to measure basic cell migration parameters such as speed, persistence, and polarity. Cells are grown to confluence and a thin "wound" introduced by scratching with a pipette tip. Cells at the wound edge polarise and migrate into the wound space. Advantages of this assay are that it does not require the use of specific chemoattractants or gradient chambers and it generates a strong directional migratory response, even in cell types that do not show robust responses in "single cell" migration assays. It is most reliably analysed when performed using time-lapse imaging, which can also yield valuable cell morphology/protein localisation information.
Clinical applications of two-dimensional electrophoresis (1995)

Two-dimensional electrophoresis is increasingly being used as an important tool for biological research although it continues to have few direct clinical applications. In the absence of simple systems to identify and quantify individual proteins or groups of proteins it is unlikely that clinical applications will increase. Measurement of some individual proteins, for example a single acute phase reactant, often yields as much clinically useful information as could be currently expected from quantitation of several proteins with the same physiological role. Cost-containment pressures within the clinical laboratory will prevent the technique from becoming widely used in the clinical laboratory until it can clearly demonstrate that it can produce clinically important and necessary information that can not be obtained by other means. We continue to believe that the technique's greatest potential lies in identifying a protein or proteins whose concentration can be correlated with a disease and whose concentration varies with the progress of the disease. Antibodies to such proteins can then be produced and used to quantify the disease-associated proteins by a simple procedure, such as nephelometry. In spite of our belief of the likely clinical application of the technique there appears to be no systematic use of two-dimensional electrophoresis for this purpose. With clinical specimens a few investigators still run gels of serum or urine from patients with apparently unusual disorders and compare them visually with gels from healthy individuals. Nevertheless, the technique continues to have considerable unmet promise for clinical applications.
Signalling role of adipose tissue: adipokines and inflammation in obesity (2005)

White adipose tissue (WAT) is a major endocrine and secretory organ, which releases a wide range of protein signals and factors termed adipokines. A number of adipokines, including leptin, adiponectin, tumour necrosis factor alpha, IL-1beta (interleukin 1beta), IL-6, monocyte chemotactic protein-1, macrophage migration inhibitory factor, nerve growth factor, vascular endothelial growth factor, plasminogen activator inhibitor 1 and haptoglobin, are linked to inflammation and the inflammatory response. Obesity is characterized by a state of chronic mild inflammation, with raised circulating levels of inflammatory markers and the expression and release of inflammation-related adipokines generally rises as adipose tissue expands (adiponectin, which has anti-inflammatory action is an exception). The elevated production of inflammation-related adipokines is increasingly considered to be important in the development of diseases linked to obesity, particularly Type II diabetes and the metabolic syndrome. WAT is involved in extensive cross-talk with other organs and multiple metabolic systems through the various adipokines.
Kinetic changes associated with load carriage using two rucksack designs (2000)

This study assessed changes in kinetics from unloaded walking associated with load carriage using both a traditional and a new rucksack design that incorporates front balance pockets (AARN). Nine subjects walked at 3(+/-0.05) km x h(-1) over a force plate unloaded and carrying 25.6 kg in each of the rucksacks. The order of trials was randomized and speed-controlled by use of photoelectric cells and a millisecond timer. Anteroposterior and vertical ground reaction forces were analyzed using repeated measures ANCOVA (speed covariate). There was a trend for the AARN pack to elicit a shorter support time than the traditional pack, 1.025+/-0.049 versus 1.037+/-0.06 s (p = 0.056), while the unloaded condition produced the shortest support time, 1.016+/-0.04 s. Both braking and propulsive forces for the rucksacks were significantly greater than for unloaded walking. While there was no significant difference between the packs for the braking force, the AARN pack produced a significantly lower (p<0.05) propulsive force than the traditional rucksack, 0.79+/-0.2 versus 0.94+/-0.16 N x kg bodyweight(-1). Both rucksacks produced significantly greater (p<0.001) vertical force peaks than unloaded walking, the increases being proportional to the increase in system weight. These findings indicate that there may be some advantage in terms of propulsive force production for the front/back system.