gebhart/patrepeval huggingface dataset:
Hypersensitization of Tumor Cells to Glycolytic Inhibitors (2001)

The slow growth of cells in the inner core of solid tumors presents a form of multidrug resistance to most of the standard chemotherapeutic agents, which target the outer more rapidly dividing cells. However, the anaerobic environment of the more centrally located tumor cells also provides an opportunity to exploit their dependence on glycolysis for therapeutic gain. We have developed two in vitro models to investigate this possibility. Model A represents osteosarcoma wild-type (wt) cells treated with agents which inhibit mitochondrial oxidative phosphorylation (Oxphos) by interacting with complexes I, III, and V of the electron transport chain in different ways, i.e., rhodamine 123 (Rho 123), rotenone, antimycin A, and oligomycin. All of these agents were found to hypersensitize wt cells to the glycolytic inhibitor 2-deoxyglucose. Cells treated with Rho 123 also become hypersensitive to oxamate, an analogue of pyruvate, which blocks the step of glycolysis that converts pyruvate to lactic acid. Model B is rho(0) cells which have lost their mitochondrial DNA and therefore cannot undergo Oxphos. These cells are 10 and 4.9 times more sensitive to 2-deoxyglucose and oxamate, respectively, than wt cells. Lactic acid levels, which are a measure of anaerobic metabolism, were found to be > 3 times higher in rho(0) than in wt cells. Moreover, when wt cells were treated with Rho 123, lactic acid amounts increased as a function of increasing Rho 123 doses. Under similar Rho 123 treatment, rho(0) cells did not increase their lactic acid levels. These data confirm that cell models A and B are similarly sensitive to glycolytic inhibitors due to their dependence on anaerobic metabolism. Overall, our in vitro results suggest that glycolytic inhibitors could be used to specifically target the slow-growing cells of a tumor and thereby increase the efficacy of current chemotherapeutic and irradiation protocols designed to kill rapidly dividing cells. Moreover, glycolytic inhibitors could be particularly useful in combination with anti-angiogenic agents, which, a priori, should make tumors more anaerobic.
High-order diffraction and diffuse reflections for interactive sound propagation in large environments (2014)

We present novel algorithms for modeling interactive diffuse reflections and higher-order diffraction in large-scale virtual environments. Our formulation is based on ray-based sound propagation and is directly applicable to complex geometric datasets. We use an incremental approach that combines radiosity and path tracing techniques to iteratively compute diffuse reflections. We also present algorithms for wavelength-dependent simplification and visibility graph computation to accelerate higher-order diffraction at runtime. The overall system can generate plausible sound effects at interactive rates in large, dynamic scenes that have multiple sound sources. We highlight the performance in complex indoor and outdoor environments and observe an order of magnitude performance improvement over previous methods.
Large scale multi-label classification via metalabeler (2009)

The explosion of online content has made the management of such content non-trivial. Web-related tasks such as web page categorization, news filtering, query categorization, tag recommendation, etc. often involve the construction of multi-label categorization systems on a large scale. Existing multi-label classification methods either do not scale or have unsatisfactory performance. In this work, we propose MetaLabeler to automatically determine the relevant set of labels for each instance without intensive human involvement or expensive cross-validation. Extensive experiments conducted on benchmark data show that the MetaLabeler tends to outperform existing methods. Moreover, MetaLabeler scales to millions of multi-labeled instances and can be deployed easily. This enables us to apply the MetaLabeler to a large scale query categorization problem in Yahoo!, yielding a significant improvement in performance.
A Convex Optimization Approach to the Rational Covariance Extension Problem (1998)

In this paper we present a convex optimization problem for solving the rational covariance extension problem. Given a partial covariance sequence and the desired zeros of the modeling filter, the poles are uniquely determined from the unique minimum of the corresponding optimization problem. In this way we obtain an algorithm for solving the covariance extension problem, as well as a constructive proof of Georgiou's seminal existence result and his conjecture, a stronger version of which we have resolved in [Byrnes et al., IEEE Trans. Automat. Control, AC-40 (1995), pp. 1841--1857].
Expression and amplification of cyclin genes in human breast cancer. (1993)

Cyclins, the regulatory subunits of cyclin-dependent kinases, play an important role in the control of cellular proliferation. Since dysregulated expression of these genes may contribute to the malignant phenotype the expression and amplification of cyclin A, B1, C, D1, D2, D3 and E genes were studied in 20 breast cancer cell lines. Increased expression of one or more of the cyclin A, B1, D1 or E genes was found in seven cell lines (35%); of these five (25%) showed increased expression of cyclin D1. Overexpression occurred in both the presence and absence of gene amplification. Conversely, amplification did not invariably lead to overexpression. Cyclin D2 expression was lower in breast cancer cell lines than in cultured normal breast epithelial cells. Cyclin D1 expression was further investigated in breast tumour biopsies: 56 of 124 specimens (45%) expressed higher levels of cyclin D1 mRNA than normal breast tissue. These data implicate dysregulated expression of several cyclin genes, particularly cyclin D1, as a potential factor in the pathogenesis of breast cancer.
Acute occlusion due to coronary dissection as a PTCA complication resolved by reentry achieved by pulling an inflated balloon in the true lumen. (1994)

We experienced 2 patients in whom conventional percutaneous methods were not useful for acute occlusions sequel to coronary angioplasty. Acute occlusions seemed to be caused by large dissections. Pulling an inflated balloon at the dissected lesions achieved reentry from the false lumen to the true lumen, thus resolving collapse of the true lumen and recanalizing the occluded coronary artery.
Phosphorylation by Glycogen Synthase Kinase-3β Down-regulates Notch Activity, a Link for Notch and Wnt Pathways (2003)

Phosphorylation of Notch proteins has been indirectly correlated with Notch activation and nuclear translocation as well as cellular transformation. There is evidence that the Wnt signaling pathway, which results in glycogen synthase kinase-3 beta (GSK-3 beta) inhibition, cross-talks with the Notch pathway. In this study, we show that GSK-3 beta is able to bind and phosphorylate Notch2 in vitro and in vivo. We identify three specific phosphorylation sites in the Notch2 serine/threonine-rich domain that are dependent on GSK-3 beta activity. Phosphorylation of the serine/threonine-rich domain has been shown previously to be crucial in regulating cytokine-specific cell differentiation. Coimmunoprecipitation experiments show that full-length Notch2 binds more efficiently than intracellular Notch2 to GSK-3 beta. Nevertheless, only the processed Notch2 is a substrate for the kinase, thus suggesting that GSK-3 beta-dependent phosphorylation may be specifically regulating the activated Notch molecule. Consistent with this, GSK-3 beta inhibits the transcriptional activation of Notch target genes both in vitro and in vivo, whereas lithium chloride treatment or Wnt-1 overexpression that results in GSK-3 beta inhibition leads to the up-regulation of the Hes-1 promoter. Together, our results suggest that cross-talk between Notch and Wnt pathways may be partially mediated by specific regulation of GSK-3 beta-dependent Notch phosphorylation.
Prevention of suction-induced gastric mucosal damage in dogs (1987)

Gastric suction has traditionally been available in three modes: continuous, sump, and intermittent. An intermittent air injection suction system (IAIS) has been developed in which small (20 to 30 mm) amounts of air are injected two to three times a minute. Very low (20 mm Hg) suction levels are applied. The hypothesis of the present study is that such a device will prevent suction-induced gastric mucosal damage, probably produced by suctioning of mucosa into the holes of the NG tube. IAIS should prevent this by physically expelling the mucosa out of the holes and allowing use of much lower suction levels. In 25 animals, gastric suction for 24 h in anesthetized dogs routinely produced ulcers. However, IAIS produced significantly fewer ulcers and in fewer animals. In 37 animals, the effectiveness of suction, measured by recovery of fluid instilled in the stomach, and the tendency of the tube to block were studied. Effectiveness was the same for all modes studied. Blockage was significantly less with IAIS.
Enzymes and auxiliary factors for GPI lipid anchor biosynthesis and post‐translational transfer to proteins (2003)

GPI lipid anchoring is an important post-translational modification of eukaryote proteins in the endoplasmic reticulum. In total, 19 genes have been directly implicated in the anchor synthesis and the substrate protein modification pathway. Here, the molecular functions of the respective proteins and their evolution are analyzed in the context of reported literature data and sequence analysis studies for the complete pathway (http://mendel.imp.univie.ac.at/SEQUENCES/gpi-biosynthesis/) and questions for future experimental investigation are discussed. Studies of two of these proteins have provided new mechanistic insights. The cytosolic part of PIG-A/GPI3 has a two-domain alpha/beta/alpha-layered structure; it is suggested that its C-terminal subsegment binds UDP-GlcNAc whereas the N-terminal domain interacts with the phosphatidylinositol moiety. The lumenal part of PIG-T/GPI16 apparently consists of a beta-propeller with a central hole that regulates the access of substrate protein C termini to the active site of the cysteine protease PIG-K/GPI8 (gating mechanism) as well as of a polypeptide hook that embraces PIG-K/GPI8. This structural proposal would explain the paradoxical properties of the GPI lipid anchor signal motif and of PIG-K/GPI8 orthologs without membrane insertion regions in some species.
Scape: supporting stereoscopic collaboration in augmented and projective environments (2004)

Our collaborative augmented reality system for multiple users simultaneously creates outside-in workbench views and inside-out life-size walkthrough views, bridging the virtual and augmented reality paradigms. Here we introduce a collaborative infrastructure - stereoscopic collaboration in augmented and projective environments(Scape). Scape seamlessly merges the paradigm of virtual reality with that of augmented reality in a single system and provides multimodality interface devices and unique widget interfaces to facilitate collaborative work in 3D environments. A custom-designed cross-platform application-programming interface (API) allows high and medium-level controls over the Scape workspace to enable augmented interaction and collaboration.
Zosteriform spread of herpes simplex virus as a model of recrudescence and its use to investigate the role of immune cells in prevention of recurrent disease (1984)

During the development of a zosteriform rash, which occurs after flank inoculation of BALB/c mice with herpes simplex virus, clinically normal skin becomes infected via nerve endings. This is analogous to the final step in the development of a recrudescent lesion, which may occur after reactivation of latent virus. Therefore, the zosteriform reaction has potential as a model with which to study the modification of such a recrudescent infection by immune processes. Using an adoptive transfer system, we confirmed that immune lymph node cells are potent in accelerating the clearance of virus from the primary site of replication (the inoculation site). This effect was T cell dependent. However, if injection of the same cell population was delayed until ganglionic infection was established, the appearance of the zosteriform rash was not prevented, and the virus titer recovered from the lower flank was not reduced. Immunoperoxidase studies showed that virus is at first highly localized to the epidermis after it emerges from nerves. As determined by conventional histology, little cellular infiltration was seen until clinical lesions were apparent. These observations indicate that recrudescent lesions appear in the presence of cell populations normally associated with rapid virus clearance; cellular immune mechanisms may be rendered ineffective owing to the lack of recruitment to the site of recrudescence until tissue breakdown instigates an inflammatory response.
Inhibition of NIH 3T3 Cell Proliferation by a Mutant ras Protein with Preferential Affinity for GDP (1988)

Substitution of asparagine for serine at position 17 decreased the affinity of rasH p21 for GTP 20- to 40-fold without significantly affecting its affinity for GDP. Transfection of NIH 3T3 cells with a mammalian expression vector containing the Asn-17 rasH gene and a Neor gene under the control of the same promoter yielded only a small fraction of the expected number of G418-resistant colonies, indicating that expression of Asn-17 p21 inhibited cell proliferation. The inhibitory effect of Asn-17 p21 required its localization to the plasma membrane and was reversed by coexpression of an activated ras gene, indicating that the mutant p21 blocked the endogenous ras function required for NIH 3T3 cell proliferation. NIH 3T3 cells transformed by v-mos and v-raf, but not v-src, were resistant to inhibition by Asn-17 p21, indicating that the requirement for normal ras function can be bypassed by these cytoplasmic oncogenes. The Asn-17 mutant represents a novel reagent for the study of ras function by virtue of its ability to inhibit cellular ras activity in vivo. Since this phenotype is likely associated with the preferential affinity of the mutant protein for GDP, analogous mutations might also yield inhibitors of other proteins whose activities are regulated by guanine nucleotide binding.
Stereocontrolled synthesis of oligonucleoside phosphorothioates and PO/PS-chimeric oligonucleotides by using oxazaphospholidine derivatives (2008)

Solid-phase synthesis of oligonucleotides having a fully-modified stereoregular phosphorothioate backbone or a stereoregular phosphate/phosphorothioate chimeric backbone was achieved by using diastereopure nucleoside 3'-bicyclic oxazaphospholidine derivatives and beta-cyanoethyl phosphoramidites as monomer units and N-(cyanomethyl)pyrrolidinium trifluoromethanesulfonate (CMPT) as an acidic activator. The trans-isomers of the oxazaphospholidines were obtained exclusively by the reaction of the 3'-OH of appropriately protected nucleosides and the corresponding 2-chloro-1,3,2-oxazaphospholidine derivative. The trans-isomers were configurationally stable and did not epimerize almost at all even in the presence of CMPT. As a result, the formation of phosphorothioate internucleotide linkages using the oxazaphospholidine derivatives and CMPT proceeded without any loss of diastereopurity. In addition to the synthesis of stereoregular phosphorothioate linkages, the synthesis of phosphate internucleotide linkages through the same method was studied. As a result of the study, stereoregular phosphate/phosphorothioate chimeric oligonucleotides as well as stereoregular oligonucleoside phosphorothioates were efficiently synthesized by using the same method.
Synthesis and Characterization of Comb-Branched Polyelectrolytes. 1. Preparation of Cationic Macromonomer of 2-(Dimethylamino)ethyl Methacrylate by Atom Transfer Radical Polymerization (2000)

The synthesis of water-soluble macromonomers of 2-(dimethylamino)ethyl methacrylate (DMAEMA) by atom transfer radical polymerization (ATRP) was studied in detail. The survival of the unsaturated groups in the initiators during the macromonomer preparation as well as the initiator efficiency depended on the nature of initiator and type of ligand used. The kinetics of the ATRP of DMAEMA catalyzed by allyl 2-bromoisobutyrate (ABIB)/copper bromide (CuBr)/N,N,N',N',N' '-pentamethyldiethylenetriamine (PMDETA) system at different conditions indicated that the low initiator efficiency of the ATRP system could not be improved by increasing temperature or changing solvents. It was found that ABIB/CuBr/tris(2-di(butylacrylate)aminoethyl)amine (BA6-TREN) and allyl trichloroacetamide (ATCA)/CuBr/BA6-TREN gave high initiator efficiencies and excellent control over the molecular weights and molecular weight distributions in the ATRP of DMAEMA. 1H NMR studies confirmed that each polyDMAEMA chain had a polymerizable allyl end group. These allyl-terminated polyDMAEMAs after quaternized were proven to be reactive in the copolymerization with acrylamide.
IUPAC-IUB Commission on Biochemical Nomenclature A One-Letter Notation for Amino Acid Sequences1–3 (1968)

Tentative Rules are printed for the benefit of those workers who have occasion to use oneletter abbreviations for amino acid residues in the course of their own work.
Toll‐Like Receptor 2–Deficient Mice Are Highly Susceptible toStreptococcus pneumoniaeMeningitis because of Reduced Bacterial Clearing and Enhanced Inflammation (2002)

Toll-like receptor-2 (TLR2) mediates host responses to gram-positive bacterial wall components. TLR2 function was investigated in a murine Streptococcus pneumoniae meningitis model in wild-type (wt) and TLR2-deficient (TLR2(-/-)) mice. TLR2(-/-) mice showed earlier time of death than wt mice (P<.02). Plasma interleukin-6 levels and bacterial numbers in blood and peripheral organs were similar for both strains. With ceftriaxone therapy, none of the wt but 27% of the TLR2(-/-) mice died (P<.04). Beyond 3 hours after infection, TLR2(-/-) mice had higher bacterial loads in brain than did wt mice, as assessed with luciferase-tagged S. pneumoniae by means of a Xenogen-CCD (charge-coupled device) camera. After 24 h, tumor necrosis factor activity was higher in cerebrospinal fluid of TLR2(-/-) than wt mice (P<.05) and was related to increased blood-brain barrier permeability (Evans blue staining, P<.02). In conclusion, the lack of TLR2 was associated with earlier death from meningitis, which was not due to sepsis but to reduced brain bacterial clearing, followed by increased intrathecal inflammation.
Theory of Mid-infrared Absorption Microspectroscopy: II. Heterogeneous Samples (2010)

Fourier transform infrared (FT-IR) spectroscopic imaging combines the specificity of optical microscopy with the spectral selectivity of vibrational spectroscopy. There is increasing recognition that the recorded data may be dependent on the optical configuration and sample morphology in addition to its local material spectral response, but a quantitative framework for predicting such dependence is lacking. Here, a theory is developed to relate recorded data to the spectral and physical properties of heterogeneous samples. The modeling approach combines optical theory through rigorous coupled wave analysis with modeling of sampling geometry and sample structure. The interplay of morphology and dispersion are systematically explored using increasingly sophisticated samples to illustrate the dependence of the detected optical intensity on the spatial sample structure. Predictions of spectral distortions arising from the sample structure are quantified, and experimental validation of the developed theory is performed using a microfabricated standard from a commercial photoresist polymer. The developed framework forms a basis for understanding sample induced distortions in spectroscopic IR microscopy and imaging.
Deep Learning at Alibaba (2017)

In this talk, I will focus on the applications and the latest development of deep learning technologies at Alibaba. More specifically, I will discuss (a) how to handle high dimensional data in DNN and its application to recommender system, (b) the development of deep learning models for transfer learning and its application to multimedia data analysis, (c) the development of combinatorial optimization techniques for DNN model compression and its application to large-scale image classification, and (d) the exploration of deep learning technique for combinatorial optimization and its application to the packing problem in shipping industry. I will conclude my talk with a discussion of new directions for deep learning that are under development at Alibaba.
Bacterial redox protein azurin, tumor suppressor protein p53, and regression of cancer (2002)

The use of live bacteria in the treatment of cancer has a long and interesting history. We report the use of a purified bacterial redox protein, azurin, that enters human cancer (melanoma UISO-Mel-2) cells and induces apoptosis. The induction of apoptosis occurs readily in melanoma cells harboring a functional tumor suppressor protein p53, but much less efficiently in p53-null mutant melanoma (UISO-Mel-6) cells. A redox-negative mutant form of azurin (M44K/M64E) demonstrates much less cytotoxicity to the UISO-Mel-2 cells than the wild-type protein. Azurin has been shown to be internalized in UISO-Mel-2 cells and is localized predominantly in the cytosol and in the nuclear fraction. In the p53-null UISO-Mel-6 cells, azurin is localized only in the cytosol. Thus, intracellular trafficking of azurin to the nucleus is p53-dependent. Azurin forms a complex with p53, thereby stabilizing it and raising its intracellular level in cytosolic, mitochondrial, and nuclear fractions. Corresponding to an increasing level of p53, an inducer of apoptosis, the level of Bax also increases in mitochondria, allowing significant release of mitochondrial cytochrome c into the cytosol, thus initiating the onset of apoptosis. The M44K/M64E mutant form of azurin, deficient in cytotoxicity, is also deficient in forming a complex with p53 and is less efficient in stabilizing p53 than wild-type azurin. Azurin has been shown to allow regression of human UISO-Mel-2 tumors xenotransplanted in nude mice and may potentially be used in cancer treatment.
Photoreversible Gelation of a Triblock Copolymer in an Ionic Liquid (2015)

The reversible micellization and sol-gel transition of block copolymer solutions in an ionic liquid (IL) triggered by a photostimulus is described. The ABA triblock copolymer employed, denoted P(AzoMA-r-NIPAm)-b-PEO-b-P(AzoMA-r-NIPAm)), has a B block composed of an IL-soluble poly(ethylene oxide) (PEO). The A block consists of a random copolymer including thermosensitive N-isopropylacrylamide (NIPAm) units and a methacrylate with an azobenzene chromophore in the side chain (AzoMA). A phototriggered reversible unimer-to-micelle transition of a dilute ABA triblock copolymer (1 wt%) was observed in an IL, 1-butyl-3-methylimidazolium hexafluorophosphate ([C4mim]PF6), at an intermediate "bistable" temperature (50 °C). The system underwent a reversible sol-gel transition cycle at the bistable temperature (53 °C), with reversible association/fragmentation of the polymer network resulting from the phototriggered self-assembly of the ABA triblock copolymer (20 wt%) in [C4 mim]PF6.