gebhart/patrepeval huggingface dataset:
Developmental regulation of telomerase activity in human fetal tissues during gestation (1997)

Telomerase is a ribonucleoprotein that adds hexanucleotide repeats (telomeres) to the ends of linear chromosomes, compensating for the loss of telomeric DNA which occurs with DNA replication. In humans, telomerase has been previously detected in germ-line tissues, blastocysts, 16-20 week old fetal tissue, and most cancers, but not in mature sperm or ova, or in most normal somatic tissues. It has been hypothesized that telomerase is suppressed during somatic development and reactivated in malignancy. To test the hypothesis that telomerase is suppressed during somatic development, human fetal tissues of 8-21 weeks gestational age were assayed for telomerase activity. All tissues expressed telomerase at the earliest ages examined. Lung, liver, spleen, and testis maintained telomerase activity through the latest age assayed, namely 21 weeks. Brain and kidney telomerase activity was present up to the 16th week and was undetectable thereafter. Heart tissue did not display activity beyond the 12th week. Lysates of heart, brain, and kidney without telomerase activity did not inhibit the activity of known telomerase-positive cells, suggesting that suppression of telomerase activity during gestational development is due to a lack of active telomerase rather than to the presence of an inhibitor. These findings demonstrate tissue-specific and developmental regulation of telomerase in the human fetus, suggesting an important role for this ribonucleoprotein in human fetal tissue differentiation and development.
Antibody isotype-specific engagement of Fcγ receptors regulates B lymphocyte depletion during CD20 immunotherapy (2006)

CD20 monoclonal antibody (mAb) immunotherapy is effective for lymphoma and autoimmune disease. In a mouse model of immunotherapy using mouse anti-mouse CD20 mAbs, the innate monocyte network depletes B cells through immunoglobulin (Ig)G Fc receptor (FcgammaR)-dependent pathways with a hierarchy of IgG2a/c>IgG1/IgG2b>IgG3. To understand the molecular basis for these CD20 mAb subclass differences, B cell depletion was assessed in mice deficient or blocked for stimulatory FcgammaRI, FcgammaRIII, FcgammaRIV, or FcR common gamma chain, or inhibitory FcgammaRIIB. IgG1 CD20 mAbs induced B cell depletion through preferential, if not exclusive, interactions with low-affinity FcgammaRIII. IgG2b CD20 mAbs interacted preferentially with intermediate affinity FcgammaRIV. The potency of IgG2a/c CD20 mAbs resulted from FcgammaRIV interactions, with potential contributions from high-affinity FcgammaRI. Regardless, FcgammaRIV could mediate IgG2a/b/c CD20 mAb-induced depletion in the absence of FcgammaRI and FcgammaRIII. In contrast, inhibitory FcgammaRIIB deficiency significantly increased CD20 mAb-induced B cell depletion by enhancing monocyte function. Although FcgammaR-dependent pathways regulated B cell depletion from lymphoid tissues, both FcgammaR-dependent and -independent pathways contributed to mature bone marrow and circulating B cell clearance by CD20 mAbs. Thus, isotype-specific mAb interactions with distinct FcgammaRs contribute significantly to the effectiveness of CD20 mAbs in vivo, which may have important clinical implications for CD20 and other mAb-based therapies.
A nuclear localization signal can enhance both the nuclear transport and expression of 1 kb DNA (1999)

Although the entry of DNA into the nucleus is a crucial step of non-viral gene delivery, fundamental features of this transport process have remained unexplored. This study analyzed the effect of linear double stranded DNA size on its passive diffusion, its active transport and its NLS-assisted transport. The size limit for passive diffusion was found to be between 200 and 310 bp. DNA of 310-1500 bp entered the nuclei of digitonin treated cells in the absence of cytosolic extract by an active transport process. Both the size limit and the intensity of DNA nuclear transport could be increased by the attachment of strong nuclear localization signals. Conjugation of a 900 bp expression cassette to nuclear localization signals increased both its nuclear entry and expression in microinjected, living cells.
The Genetic Basis of Immunoglobulin-Class Switching (1994)

In the immune response to a foreign protein, the first antibodies to appear are of the IgM class (or isotype). As the response proceeds, other isotypes (IgG, IgA, and IgE) emerge as the result of immunoglobulin-class switching. The isotype switch has considerable clinical importance because each of the four major isotypes has specialized biologic properties. IgG, for example, is the principal class of antibody in interstitial fluids, whereas IgA is the protective antibody of mucosal surfaces. Isotype switching requires collaboration between antibody-synthesizing B cells and helper CD4+ T cells. In this collaboration, the B cell uses IgM molecules on its . . .
Histological evaluation of decellularised porcine aortic valves: matrix changes due to different decellularisation methods (2005)

Chemically induced decellularisation by Triton or Trypsine resulted in changes in the extracellular matrix constitution, which could lead to problems in valve functionality and cell growth and migration. Seeded endothelial cells were capable of synthesising extracellular matrix components lost by cell extraction. Further studies on tissue engineering should focus more on the effect of chemically induced cell extraction on the extracellular matrix of the remaining scaffold and the in vitro or in vivo replenishment of lost compounds.
CaMKII promotes TLR-triggered proinflammatory cytokine and type I interferon production by directly binding and activating TAK1 and IRF3 in macrophages (2008)

Calcium and its major downstream effector, calcium/calmodulin-dependent protein kinase II (CaMKII), are found to be important for the functions of immune cells. Lipopolysaccharide (LPS) has been shown to induce intracellular calcium release in macrophages; however, whether and how CaMKII is required for Toll-like receptor (TLR) signaling remain unknown. Here we demonstrate that TLR 4, 9, and 3 ligands markedly induce intracellular calcium fluxes and activate CaMKII-alpha in macrophages. Selective inhibition or RNA interference of CaMKII significantly suppresses TLR4, 9, 3-triggered production of interleukin-6 (IL-6), tumor necrosis factor-alpha, and interferon-alpha/beta (IFN-alpha/beta) in macrophages. Coincidently, overexpression of constitutively active CaMKII-alpha significantly enhances production of the above cytokines. In addition to the activation of mitogen-activated protein kinase and nuclear factor kappaB pathways, CaMKII-alpha can directly bind and phosphorylate transforming growth factor beta-activated kinase 1 (TAK1) and IFN regulatory factor 3 (IRF3; serine on 386) via the N-terminal part of its regulatory domain. Therefore, CaMKII can be activated by TLR ligands, and in turn promotes both myeloid differentiating factor 88 and Toll/IL-1 receptor domain-containing adaptor protein-inducing IFN-beta-dependent inflammatory responses by directly activating TAK1 and IRF3. The cross-talk with the calcium/CaMKII pathway is needed for full activation of TLR signaling in macrophages.
Improving the Error Back-Propagation Algorithm for Imbalanced Data Sets (2012)

Imbalanced data sets are difficult to be classified since most classifiers are developed based on the assumption that class distributions are well-balanced. In order to improve the error back-propagation algorithm for the classification of imbalanced data sets, a new error function is proposed. The error function controls weight-updating with regards to the classes in which the training samples are. This has the effect that samples in the minority class have a greater chance to be classified but samples in the majority class have a less chance to be classified. The proposed method is compared with the two-phase, threshold-moving, and target node methods through simulations in a mammography data set and the proposed method attains the best results.
Holographic Imagery Through Diffusing Media (1966)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text Emmett N. Leith and Juris Upatnieks, "Holographic Imagery Through Diffusing Media," J. Opt. Soc. Am. 56, 523-523 (1966) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Dynamic partial-order reduction for model checking software (2005)

We present a new approach to partial-order reduction for model checking software. This approach is based on initially exploring an arbitrary interleaving of the various concurrent processes/threads, and dynamically tracking interactions between these to identify backtracking points where alternative paths in the state space need to be explored. We present examples of multi-threaded programs where our new dynamic partial-order reduction technique significantly reduces the search space, even though traditional partial-order algorithms are helpless.
Angiogenesis inhibition in solid tumors. (2002)

Angiogenesis plays a central role in a variety of physiologic and pathologic disease states. Because the growth and metastasis of malignant neoplasms require the presence of an adequate blood supply, pharmacologic inhibition of tumor-induced angiogenesis represents a promising target for antineoplastic therapy. A number of approaches to such inhibition are therefore under active investigation. Vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 are among the best characterized of the various key elements in benign and neoplastic angiogenesis. In 1997, clinical trials were initiated to evaluate an anti-VEGF monoclonal antibody and a VEGFR-2 antagonist as therapy for patients with different types of solid tumors and hematologic neoplasms. Dose selection for these cytostatic agents requires translation from preclinical models, as these agents are likely to require chronic dosing at an optimal biological dose, rather than a maximally tolerated dose. For example, SU5416, a novel small-molecule inhibitor of VEGFR-2, administered at 145 mg/m2 intravenously twice weekly, is well tolerated and achieves the concentration levels required to inhibit endothelial cell proliferation in preclinical models. Because the mechanism of action of angiogenesis inhibitors is complementary to that of classic cytotoxic chemotherapy, preclinical models and subsequent clinical trials frequently explore combinations of these agents with cytotoxic chemotherapy, hoping to achieve additive or synergistic antitumor activity. It is hoped that the combination of angiogenesis inhibitors with cytotoxic chemotherapeutic agents will significantly improve survival and quality of life for cancer patients. As a result of favorable results from Phase 1 and 2 studies, randomized, multicenter clinical investigations of angiogenesis inhibitors are ongoing.
Discovering the Mechanism of Action of Novel Antibacterial Agents through Transcriptional Profiling of Conditional Mutants (2005)

We present a new strategy for predicting novel antibiotic mechanisms of action based on the analysis of whole-genome microarray data. We first built up a reference compendium of Bacillus subtilis expression profiles induced by 14 different antibiotics. This data set was expanded by adding expression profiles from mutants that showed downregulation of genes coding for proven or emerging antibacterial targets. Here, we investigate conditional mutants underexpressing ileS, pheST, fabF, and accDA, each of which is essential for growth. Our proof-of-principle analyses reveal that conditional mutants can be used to mimic chemical inhibition of the corresponding gene products. Moreover, we show that a statistical data analysis combined with thorough pathway and regulon analysis can pinpoint the molecular target of uncharacterized antibiotics. We apply this approach to two novel antibiotics: a recently published phenyl-thiazolylurea derivative and the natural product moiramide B. Our results support recent findings suggesting that the phenyl-thiazolylurea derivative is a novel phenylalanyl-tRNA synthetase inhibitor. Finally, we propose a completely novel antibiotic mechanism of action for moiramide B based on inhibition of the bacterial acetyl coenzyme A carboxylase.
Spam: the plague of junk E-mail (1998)

In a sketch on the British comedy show Monty Python's Flying Circus, a group of Vikings in a cafe sing loudly about Spam (the luncheon meat), drowning out the conversation of other diners. On the Internet, the word spam is used to mean intrusive messages, most of them commercial, that can overwhelm discussion groups and E-mail in-boxes. If you've ever posted a message on Usenet, put your E-mail address on a Web page, or even subscribed to an E-mail discussion list that wasn't configured to conceal its subscribers' addresses, chances are good that you've received unsolicited bulk E-mail, the type of spam that's generating the most controversy nowadays. Such junk E-mail is used by businesses that don't care about their reputations, so it advertises mainly questionable medical products, get-rich-quick schemes, pornography, and the like, as well as spamming software and address lists. Once you've been put on a spammer's list, it's almost impossible to get off, and the spam is likely to multiply.
Use of anti-idiotypic antibodies as cell-surface receptor probes (1978)

Anti-idiotypic antibodies have been raised against antibodies to retinol-binding protein (RBP) and to insulin. After absorption the anti-idiotypic antibodies recognized the antigen-combining sites of the antibodies used as the immunogen but of no other antibodies. Some of the anti-idiotypic antibodies raised against antibodies to RBP bound specifically to rat intestine epithelial cells, which have a physiological cell-surface receptor for RBP. The RBP receptor mediates the uptake of retinol from RBP to the cells. This uptake was abolished in a concentration-dependent manner by the anti-idiotypic antibodies, which obviously competed with RBP for binding to the receptor.Anti-idiotypic antibodies against antibodies to insulin inhibited the binding of (125)I-labeled insulin to isolated rat epididymal fat cells, whereas anti-idiotypic antibodies raised against antibodies to RBP had no effect. Furthermore, on interacting with young rat thymocytes, anti-idiotypic antibodies against antibodies to insulin stimulated the uptake by the cells of alpha-aminoisobutyric acid, thereby mimicking the effect of insulin. These results suggest that in some cases anti-idiotypic antibodies may be useful tools in elucidating structure-function relationships for cell-membrane receptors.
Generation of large-volume, atmospheric-pressure, nonequilibrium plasmas (2000)

A review is presented of the issues associated with the generation of large-volume, high-pressure, nonequilibrium plasmas, as well as the approaches that have been developed for generating these plasmas using electrical discharges in gases. The various instabilities that have been overcome to obtained these plasmas as well as the techniques for quenching them are also reviewed. Last, recent efforts to obtain atmospheric pressure plasmas are discussed with particular emphasis on the capillary plasma electrode discharge, which we have used to obtain high (electron) density nonequilibrium plasmas.
Identification of distinct cytoplasmic targets for ras/R-ras and rho regulatory proteins (1989)

The protein products of the mammalian ras genes, p21ras, are regulatory guanine nucleotide binding proteins that are involved in the control of cell proliferation, though the exact biochemical processes regulated are unknown. Recently a cytoplasmic protein has been identified that interacts with and increases the GTPase activity of p21ras. It has been shown that this GTPase-activating protein, or GAP, interacts with the effector domain of ras, leading us and others to propose that GAP may be the target for regulation by p21ras. It has become apparent that ras is part of a much larger family of proteins, and at least 15 ras-related genes have now been identified in the mammalian genome. Each encodes a small (about 21 kDa) guanine nucleotide binding protein, but the functions of none of these regulatory molecules are known. We report here that mammalian cytoplasmic extracts contain GAP-like activity toward the products of two other ras-related genes, R-ras and rho. It appears that p23R-ras interacts with the same 125-kDa GAP protein as p21ras whereas p21rho interacts with a distinct 29-kDa protein, rho GAP.
Paired β-sheet structure of an Aβ(1-40) amyloid fibril revealed by electron microscopy (2008)

Alzheimer's disease is a neurodegenerative disorder that is characterized by the cerebral deposition of amyloid fibrils formed by Abeta peptide. Despite their prevalence in Alzheimer's and other neurodegenerative diseases, important details of the structure of amyloid fibrils remain unknown. Here, we present a three-dimensional structure of a mature amyloid fibril formed by Abeta(1-40) peptide, determined by electron cryomicroscopy at approximately 8-A resolution. The fibril consists of two protofilaments, each containing approximately 5-nm-long regions of beta-sheet structure. A local twofold symmetry within each region suggests that pairs of beta-sheets are formed from equivalent parts of two Abeta(1-40) peptides contained in each protofilament. The pairing occurs via tightly packed interfaces, reminiscent of recently reported steric zipper structures. However, unlike these previous structures, the beta-sheet pairing is observed within an amyloid fibril and includes significantly longer amino acid sequences.
Characterization of Secretory Genes ypt1 / yptA and nsf1 / nsfA from Two Filamentous Fungi: Induction of Secretory Pathway Genes of Trichoderma reesei under Secretion Stress Conditions (2004)

Two genes involved in protein secretion, encoding the Rab protein YPT1/YPTA and the general fusion factor NSFI/NSFA, were characterized from two filamentous fungi, Trichoderma reesei and Aspergillus niger var. awamori. The isolated genes showed a high level of conservation with their Saccharomyces cerevisiae and mammalian counterparts, and T. reesei ypt1 was shown to complement yeast Ypt1p depletion. The transcriptional regulation of the T. reesei ypt1, nsf1, and sar1 genes, involved in protein trafficking, was studied with mycelia treated with the folding inhibitor dithiothreitol (DTT) and with brefeldin A, which inhibits membrane traffic between the endoplasmic reticulum and Golgi complex. The well-known inducer of the yeast and T. reesei unfolded protein response (UPR), DTT, induced the nsf1 gene and the protein disulfide isomerase gene, pdi1, in both of the experiments, and sar1 mRNA increased in only one experiment under strong UPR induction. The ypt1 mRNA did not show a clear increase during DTT treatment. Brefeldin A strongly induced pdi1 and all of the intracellular trafficking genes studied. These results suggest the possibility that the whole secretory pathway of T. reesei could be induced at the transcriptional level by stress responses caused by protein accumulation in the secretory pathway.
Physical properties of solid dispersions of poorly water-soluble drugs with enteric coating agents. (1985)

Enteric coating agents, such as hydroxypropylmethylcellulose phthalate, methacrylic acidmethacrylic acid methyl ester copolymer, cellulose acetate phthalate, carboxymethylethylcellulose, were investigated as possible carriers for poorly water-soluble drugs in solid dispersions. In most cases, the drugs were present in amorphous form in the solid dispersions of 1 : 3 weight ratio of drug to polymer, though griseofulvin and phenytoin were not. Dissolution behavior was investigated using nifedipine, griseofulvin or spironolactone as a drug. The amorphous solid dispersions showed supersaturation phenomena in JPX 2nd fluid (pH 6.8), but the dissolution rate was suppressed in JPX 1st fluid (pH 1.2). It was confirmed that the physicochemical state of solid dispersions plays a predominant role in the dissolution of the drug from the solid dispersions.
Advances in smart antennas - Network coordination for spectrally efficient communications in cellular systems (2006)

In this article we consider network coordination as a means to provide spectrally efficient communications in cellular downlink systems. When network coordination is employed, all base antennas act together as a single network antenna array, and each mobile may receive useful signals from nearby base stations. Furthermore, the antenna outputs are chosen in ways to minimize the out-of-cell interference, and hence to increase the downlink system capacity. When the out-of-cell interference is mitigated, the links can operate in the high signal-to-noise ratio regime. This enables the cellular network to enjoy the great spectral efficiency improvement associated with using multiple antennas
A 19.4 dBm, Q-Band Class-E Power Amplifier in a 0.12 <formula formulatype="inline"><tex Notation="TeX">$\mu {\rm m}$</tex> </formula> SiGe BiCMOS Process (2010)

A Q-band, Class-E power amplifier has been designed and fabricated in a 0.12 μm SiGe BiCMOS technology. The amplifier was designed for high output power using on-chip power combining networks. It operates respectively from a 1.2 V supply for peak efficiency and a 2.4 V supply for maximum power and occupies an area of 0.801 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . A peak PAE of 18% is measured for an output power of 11.3 dBm at 45 GHz and a maximum <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">P</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">sat</sub> of 19.4 dBm is measured at 42 GHz with a PAE of 14.4%. The power amplifier operates from 42 to 50 GHz.
Novel “hybrid” iron chelators derived from aroylhydrazones and thiosemicarbazones demonstrate selective antiproliferative activity against tumor cells (2002)

We previously demonstrated that 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) and other aroylhydrazone chelators possess potent antineoplastic activity because of their ability to bind iron (Fe). From these studies, we identified structural components of the hydrazones that provide antineoplastic activity, namely the salicylaldehyde and 2-hydroxy-1-naphthylaldehyde moieties. A related group of chelators known as the thiosemicarbazones also show pronounced antitumor activity because of their ability to inhibit ribonucleotide reductase. Considering this, we designed a new series of "hybrid ligands" by condensation of the aldehydes described above with a range of thiosemicarbazides. The parent compound of these ligands is 2-hydroxy-1-naphthylaldehyde thiosemicarbazone (NT). Of 8 NT analogues, 3 chelators, namely NT, N4mT (2-hydroxy-1-naphthylaldehyde-4-methyl-3-thiosemicarbazone), and N44mT (2-hydroxy-1-naphthylaldehyde-4,4-dimethyl-3-thiosemicarbazone), showed high antiproliferative activity against SK-N-MC neuroepithelioma cells (50% inhibitory concentration [IC(50)] = 0.5-1.5 microM). Indeed, their activity was significantly (P <.0001) greater than that of desferrioxamine (DFO) (IC(50) = 22 microM). We demonstrate that 311, a 311 analogue (311m), and several NT-series chelators have significantly (P <.001) greater antiproliferative activity against tumor cells than against a range of normal cell types. For example, the IC(50) values of NT and N4mT in SK-N-MC neuroepithelioma cells were 0.5 microM, whereas for fibroblasts the IC(50) values were greater than 25 microM. Further, the effect of one of the most potent chelators (311m) on preventing the growth of bone marrow stem cell cultures was far less than that of doxorubicin and similar to that of cisplatin. These studies support the further development of these chelators as antiproliferative agents.