gebhart/patrepeval huggingface dataset:
Nuclear cyclin B1 in human breast carcinoma as a potent prognostic factor (2007)

Cyclin B1 is translocated to the nucleus from the cytoplasm, and plays an essential role in cell proliferation through promotion of mitosis. Although overexpression of cyclin B1 was previously reported in breast carcinomas, the biological significance of the intracellular localization of cyclin B1 remains unclear. Therefore, in this study, we examined cyclin B1 immunoreactivity in 109 breast carcinomas, according to the intracellular localization, that is, nucleus, cytoplasm or total (nucleus or cytoplasm). Total cyclin B1 was detected in carcinoma cells in 42% of breast carcinomas examined, whereas nuclear and cytoplasmic cyclin B1 were positive in 17 and 35% of the cases, respectively. Total or cytoplasmic cyclin B1 were positively associated with histological grade, mitosis, Ki-67, p53, c-myc or 14-3-3sigma, and inversely correlated with estrogen or progesterone receptor. Nuclear cyclin B1 was significantly associated with tumor size, lymph node metastasis, histological grade, mitosis, Ki-67 or polo-like kinase 1. Only nuclear cyclin B1 was significantly associated with adverse clinical outcome of the patients, and multivariate analyses of disease-free and overall survival demonstrated nuclear cyclin B1 as the independent marker. A similar tendency was detected in the patients receiving adjuvant therapy after surgery. These results suggest that an onocogenic role of overexpressed cyclin B1 is mainly mediated in nuclei of breast carcinoma cells, and the nuclear translocation is regulated by polo-like kinase 1 and 14-3-3sigma. Nuclear cyclin B1-positive breast carcinoma is resistant to adjuvant therapy, and nuclear cyclin B1 immunoreactivity is a potent prognostic factor in breast carcinoma patients.
Suppression of cellular aggregation by high levels of episialin. (1992)

Episialin is a mucin-like molecule located at the apical surface of most glandular epithelial cells. It is present at increased levels in carcinomas, where the molecule is often distributed over the entire cell surface. We have simulated this overproduction of episialin by transfecting a normal mammary epithelial cell line and a melanoma cell line with full-length complementary DNA encoding episialin. Transfectants of both cell lines containing episialin at levels similar to that of carcinoma cell lines do not aggregate as efficiently as their control cells, which do not express exogenous episialin. In mixing experiments, episialin transfectants are excluded from aggregates formed by these control cells, indicating that high levels of episialin on one of the interacting cells is sufficient to inhibit aggregation. The effect of episialin overexpression on aggregation is probably not only due to the negative charge of its numerous sialic acid residues, since neuraminidase treatment only partially restored the aggregation capacity of the transfectants. We propose that episialin, as a result of its large, extended, and rigid structure, can mask most cell surface molecules in its immediate surroundings and that a high density of episialin can severely disturb the interaction of cell surface proteins with macromolecules on adjacent cell membranes.
Molecular dissection of bacterial acrylate catabolism – unexpected links with dimethylsulfoniopropionate catabolism and dimethyl sulfide production (2009)

A bacterium in the genus Halomonas that grew on dimethylsulfoniopropionate (DMSP) or acrylate as sole carbon sources and that liberated the climate-changing gas dimethyl sulfide in media containing DMSP was obtained from the phylloplane of the macroalga Ulva. We identified a cluster that contains genes specifically involved in DMSP catabolism (dddD, dddT) or in degrading acrylate (acuN, acuK) or that are required to break down both substrates (dddC, dddA). Using NMR and HPLC analyses to trace 13C- or 14C-labelled acrylate and DMSP in strains of Escherichia coli with various combinations of cloned ddd and/or acu genes, we deduced that DMSP is imported by the BCCT-type transporter DddT, then converted by DddD to 3-OH-propionate (3HP), liberating dimethyl sulfide in the process. As DddD is a predicted acyl CoA transferase, there may be an earlier, unidentified catabolite of DMSP. Acrylate is also converted to 3HP, via a CoA transferase (AcuN) and a hydratase (AcuK). The 3HP is predicted to be catabolized by an alcohol dehydrogenase, DddA, to malonate semialdehyde, thence by an aldehyde dehydrogenase, DddC, to acyl CoA plus CO2. The regulation of the ddd and acu genes is unusual, as a catabolite, 3HP, was a co-inducer of their transcription. This first description of genes involved in acrylate catabolism in any organism shows that the relationship between the catabolic pathways of acrylate and DMSP differs from that which had been suggested in other bacteria.
Stereospecific CO2 Copolymers from 3,5-Dioxaepoxides: Crystallization and Functionallization (2014)

Selective transformation of CO2 into biodegradable polycarbonates (CO2-based copolymers) by the alternating copolymerization with epoxides represents a most promising green polymerization process. Despite the tremendous progress this field has made, most of the CO2-based polycarbonates are known to be amorphous, and their low thermal resistance makes them difficult to use as structural materials. Herein, we report the selective synthesis of highly isotactic CO2 copolymers from meso-3,5-dioxaepoxides in perfectly alternating nature by the enantiopure dinuclear Co(III)-complex-mediated desymmetrization copolymerization under mild conditions. These isotactic CO2-based polycarbonates are typical semicrystalline polymers, possessing melting points (Tm) of 179–257 °C, dependent on the substitute groups at 4-position of the meso-epoxides. As a model monomer of 3,5-dioxa-epoxides, 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane (CXO) was studied in detail in the asymmetric copolymerization with CO2. The isotactic CO2/CXO copolymer (PCXC) with >99% enantioselectivity possesses a high Tm of 242 °C and a decomposition temperature of 320 °C, while its atactic copolymer has a high Tg of up to 140 °C. Moreover, the acid hydrolysis of highly isotactic PCXC was performed to provide stereoregular poly(1,2-bis(hydroxymethyl)ethylene carbonate)s (PCFC) with two hydroxyl groups in a carbonate unit, which showed a remarkable decrease of ∼80 °C in thermal decomposition temperature. This hydroxyl-functionalized CO2 copolymer accords with an unmet need for a readily degradable biocompatible polycarbonate and was further explored to prepare bush copolymers for biomedical and pharmaceutical applications. This approach was initially demonstrated by the hydroxyl groups appended in polycarbonate backbone of a hydroxyl-functionalized terpolymer serving as macroinitiators for direct graft polymerization via organocatalytic lactide ring-opening polymerization to give fully degradable brush polymers with polycarbonate backbones and polylactide side chains. Furthermore, enantiopure dinuclear Co(III)-complex-mediated asymmetric terpolymerization of CO2 with CXO and cyclohexene oxide (CHO) at various feed ratios was carried out in toluene solution, affording optically active terpolymers poly(CHC-co-CXC) with highly enantioselective ring-opening of the both meso-epoxides. These stereospecific terpolymers were found to be crystallizable and their crystallization capacity could be tuned by changing the feed ratio of the epoxides.
Sulfonylurea Stimulation of Insulin Secretion (2002)

Sulfonylureas are widely used to treat type 2 diabetes because they stimulate insulin secretion from pancreatic beta-cells. They primarily act by binding to the SUR subunit of the ATP-sensitive potassium (K(ATP)) channel and inducing channel closure. However, the channel is still able to open to a limited extent when the drug is bound, so that high-affinity sulfonylurea inhibition is not complete, even at saturating drug concentrations. K(ATP) channels are also found in cardiac, skeletal, and smooth muscle, but in these tissues are composed of different SUR subunits that confer different drug sensitivities. Thus tolbutamide and gliclazide block channels containing SUR1 (beta-cell type), but not SUR2 (cardiac, smooth muscle types), whereas glibenclamide, glimepiride, repaglinide, and meglitinide block both types of channels. This difference has been exploited to determine residues contributing to the sulfonylurea-binding site. Sulfonylurea block is decreased by mutations or agents (e.g., phosphatidylinositol bisphosphate) that increase K(ATP) channel open probability. We now propose a kinetic model that explains this effect in terms of changes in the channel open probability and in the transduction between the drug-binding site and the channel gate. We also clarify the mechanism by which MgADP produces an apparent increase of sulfonylurea efficacy on channels containing SUR1 (but not SUR2).
Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands (2012)

Autocrine and paracrine cell communication can be conveyed by multiple mediators, including membrane-associate proteins, secreted proteins and exosomes. Exosomes are 30-100 nm endosome-derived vesicles consisting in cytosolic material surrounded by a lipid bilayer containing transmembrane proteins. We have previously shown that dendritic cells (DCs) express on their surface multiple TNF superfamily ligands (TNFSFLs), by which they can induce the apoptotic demise of tumor cells as well as the activation of natural killer (NK) cells. In the present study, we demonstrate that, similar to DCs, DC-derived exosomes (DCex) express on their surface TNF, FasL and TRAIL, by which they can trigger caspase activation and apoptosis in tumor cells. We also show that DCex activate NK cells and stimulate them to secrete interferonγ (IFNγ) upon the interaction of DCex TNF with NK-cell TNF receptors. These data demonstrate that DCex can mediate essential innate immune functions that were previously ascribed to DCs.
X-ray crystal structure of the human dimeric S-Lac lectin, L-14-II, in complex with lactose at 2.9-A resolution. (1993)

S-Lac lectins are a family of soluble lactose-binding animal lectins, some of which have been implicated in modulating cell-cell and cell-matrix interactions through specific carbohydrate-mediated recognition. We report here the x-ray crystal structure of a representative member of this family, the human dimeric S-Lac lectin, L-14-II, in complex with lactose, at 2.9-A resolution. The two-fold symmetric dimer is made up of two extended anti-parallel beta-sheets, which associate in a beta-sandwich motif. Remarkably, the L-14-II monomer shares not only the same topology, but a very similar beta-sheet structure with that of the leguminous plant lectins, suggesting a conserved structure-function relationship. Carbohydrate binding by L-14-II was found to involve protein residues that are very highly conserved among all S-Lac lectins. These residues map to a single DNA exon, suggesting a carbohydrate binding cassette common to all S-Lac lectins.
Drug delivery to the inner ear (2012)

Bionic devices electrically activate neural populations to partially restore lost function. Of fundamental importance is the functional integrity of the targeted neurons. However, in many conditions the ongoing pathology can lead to continued neural degeneration and death that may compromise the effectiveness of the device and limit future strategies to improve performance. The use of drugs that can prevent nerve cell degeneration and promote their regeneration may improve clinical outcomes. In this paper we focus on strategies of delivering neuroprotective drugs to the auditory system in a way that is safe and clinically relevant for use in combination with a cochlear implant. The aim of this approach is to prevent neural degeneration and promote nerve regrowth in order to improve outcomes for cochlear implant recipients using techniques that can be translated to the clinic.
Competition and Coexistence betweenStreptococcus mutansandStreptococcus sanguinisin the Dental Biofilm (2005)

The human mucosal surface is colonized by the indigenous microflora, which normally maintains an ecological balance among different species. Certain environmental or biological factors, however, may trigger disruption of this balance, leading to microbial diseases. In this study, we used two oral bacterial species, Streptococcus mutans and Streptococcus sanguinis (formerly S. sanguis), as a model to probe the possible mechanisms of competition/coexistence between different species which occupy the same ecological niche. We show that the two species engage in a multitude of antagonistic interactions temporally and spatially; occupation of a niche by one species precludes colonization by the other, while simultaneous colonization by both species results in coexistence. Environmental conditions, such as cell density, nutritional availability, and pH, play important roles in determining the outcome of these interactions. Genetic and biochemical analyses reveal that these interspecies interactions are possibly mediated through a well-regulated production of chemicals, such as bacteriocins (produced by S. mutans) and hydrogen peroxide (produced by S. sanguinis). Consistent with the phenotypic characteristics, production of bacteriocins and H2O2 are regulated by environmental conditions, as well as by juxtaposition of the two species. These sophisticated interspecies interactions could play an essential part in balancing competition/coexistence within multispecies microbial communities.
Association of Phospholipase D Activity with the Detergent-insoluble Cytoskeleton of U937 Promonocytic Leukocytes (1999)

Phospholipase D (PLD) regulates cytoskeletal-dependent antimicrobial responses of myeloid leukocytes, including phagocytosis and oxidant generation. However, the mechanisms responsible for this association between PLD activity and the actin cytoskeleton are unknown. We utilized a cell-free system from U937 promonocytes to test the hypothesis that stimulation of PLD results in stable association of the activated lipase with the detergent-insoluble membrane skeleton. Plasma membrane and cytosol were incubated +/- guanosine 5'-3-O-(thio)triphosphate (GTPgammaS), followed by re-isolation and extraction of the washed membranes with octyl glucoside. The detergent-insoluble fraction derived from membranes incubated with GTPgammaS (DIFGTPgammaS) exhibited 22-fold greater PLD activity than that derived from control membranes (DIF0), when both were assayed in the presence of GTPgammaS. The DIF contained PLD1, RhoA, and ARF, and the level of each was increased by GTPgammaS in a dose-dependent manner. The DIF also contained F-actin, vinculin, talin, paxillin, and alpha-actinin, consistent with its identification as the membrane skeleton. The physiologic relevance of these findings was demonstrated by a similar increase in DIF-associated PLD activity after stimulation of intact U937 cells with opsonized zymosan. These results indicate that stimulation of PLD1 is accompanied by stable association of the activated lipase, RhoA, and ADP-ribosylation factor with the actin-based membrane skeleton.
DNA vaccines to attack cancer (2004)

Delivery of antigens by injection of the encoding DNA allows access to multiple antigen-presenting pathways. Knowledge of immunological processes can therefore be used to modify construct design to induce selected effector functions. Expression can be directed to specific intracellular sites, and additional genes can be fused or codelivered to amplify responses. Therapeutic vaccination against cancer adds a requirement to overcome tolerance and to activate a weakened immune repertoire. Induction of CD4(+) T helper cells is critical for both antibody and T cell effector responses. To activate immunity against tumor antigens, we fused the tumor-derived sequences to genes encoding microbial proteins. This strategy engages T helper cells from the large antimicrobial repertoire for linked help for inducing antibody against cell-surface tumor antigens. The principle of linked T cell help also holds for induction of epitope-specific antitumor CD8(+) T cells, but the microbial sequence has to be minimized to avoid competition with tumor antigens. Epitope-specific DNA vaccination leads to powerful antitumor attack and can activate immunity from a profoundly tolerized repertoire. Vaccine designs validated in preclinical models are now in clinical trial with immune responses detected against both tumor antigens and fused microbial antigens. DNA priming is highly efficient, but boosting may benefit from increased antigen expression. Physical methods including electroporation provide increased expression without introducing additional competing antigens. A wide range of cancers can be targeted, and objective assays of response will determine efficacy.
Multi-language text indexing for internet retrieval (1997)

We address here the issues associated with indexing multilingual collections of information, as is found for example on the internet. We examine in particular the task of language identification and the use of stemming algorithms for several European languages. We also present the lessons we have learned from our experience in using the SPIDER information retrieval system as a search engine over the intranet of the ETH Zurich; a multilingual intranet which contains documents in English, French, German and Italian.
The influence of single base triplet changes on the stability of a Pur·Pur·Pyr triple helix determined by affinity cleaving (1992)

The influence of sixteen base triplet changes at a single position within a pur.pur.pyr triple helix was examined by affinity cleaving. For the 15 base pair target site studied here, G.GC, A.AT and T.AT triplets stabilize a triple helix to a greater extent than the other 13 natural triplets (pH = 7.4, 25 degrees C). Weaker interactions were detected for the C.AT, A.GC and T.CG triplets. The absence of specific, highly stabilizing interactions between third strand bases and the CG or TA base pairs demonstrates a current sequence limitation to formation of this structure. Models for the two dimensional base triplet interactions for all possible 16 natural triplets are presented.
An NCR1-based chimeric receptor endows T-cells with multiple anti-tumor specificities (2014)

The Ral (Ras-like) GTP-binding proteins (RalA and RalB), as effectors of the proto-oncogene Natural killer (NK) cells are an important component of the anti-tumor response. Tumor recognition by NK cells was found to be partly triggered by molecules termed natural cytotoxic receptors (NCRs). Adoptive transfer of genetically-engineered tumor-reactive T-lymphocytes can mediate remarkable tumor regressions mostly in melanoma and leukemia patients. Yet, the application of such treatments to other cancers is needed and dependent on the isolation of receptors that could facilitate efficient recognition of these malignancies. Herein, we aimed at combining NK tumor recognition capability with the genetic modification of T-cells to provide the latter with a means to recognize several tumors in a non-MHC restricted way. Consequently, we generated and evaluated several chimeric receptors based on the extracellular domain of NCR1 (NKp46) fused to multiple signaling moieties and assess their antitumor activity when retrovirally expressed in T-cells. Following co-culture with different tumors, primary human T-lymphocytes expressing a chimeric NCR1 molecule recognized target cells derived from lung, cervical carcinoma, leukemia and pancreatic cancer. In addition, this receptor mediated an upregulation of surface activation markers and significant antitumor cytotoxicity both in vitro and in vivo. These results have meaningful implications for the immunotherapeutic treatment of cancer using gene-modified T-cells.
Silicon‐Based Nanomaterials for Lithium‐Ion Batteries: A Review (2013)

There are growing concerns over the environmental, climate, and health impacts caused by using non‐renewable fossil fuels. The utilization of green energy, including solar and wind power, is believed to be one of the most promising alternatives to support more sustainable economic growth. In this regard, lithium‐ion batteries (LIBs) can play a critically important role. To further increase the energy and power densities of LIBs, silicon anodes have been intensively explored due to their high capacity, low operation potential, environmental friendliness, and high abundance. The main challenges for the practical implementation of silicon anodes, however, are the huge volume variation during lithiation and delithiation processes and the unstable solid‐electrolyte interphase (SEI) films. Recently, significant breakthroughs have been achieved utilizing advanced nanotechnologies in terms of increasing cycle life and enhancing charging rate performance due partially to the excellent mechanical properties of nanomaterials, high surface area, and fast lithium and electron transportation. Here, the most recent advance in the applications of 0D (nanoparticles), 1D (nanowires and nanotubes), and 2D (thin film) silicon nanomaterials in LIBs are summarized. The synthetic routes and electrochemical performance of these Si nanomaterials, and the underlying reaction mechanisms are systematically described.
Decentralized charging control for large populations of plug-in electric vehicles (2010)

The paper develops a novel decentralized charging control strategy for large populations of plug-in electric vehicles (PEVs). We consider the situation where PEV agents are rational and weakly coupled via their operation costs. At an established Nash equilibrium, each of the PEV agents reacts optimally with respect to the average charging strategy of all the PEV agents. Each of the average charging strategies can be approximated by an infinite population limit which is the solution of a fixed point problem. The control objective is to minimize electricity generation costs by establishing a PEV charging schedule that fills the overnight demand valley. The paper shows that under certain mild conditions, there exists a unique Nash equilibrium that almost satisfies that goal. Moreover, the paper establishes a sufficient condition under which the system converges to the unique Nash equilibrium. The theoretical results are illustrated through various numerical examples.
The neurological complications of sepsis (1993)

Encephalopathy and polyneuropathy occur in 70% of septic patients. The encephalopathy is diffuse, appears early, is often severe, but reverses quickly with successful treatment of the sepsis. The electroencephalogram is a sensitive indicator of the incidence and severity of the encephalopathy, but computed tomograms of the brain and cerebrospinal fluid findings are unremarkable. Critical-illness polyneuropathy develops later and in association with multiple-organ failure. Recovery is more gradual. Difficulty in weaning from the ventilator is an important early manifestation. Electromyography should be routinely performed to establish the diagnosis. The polyneuropathy is a primary axonal degeneration, predominantly of distal motor fibers. A persistent deficit may eventuate in severe cases. Whether muscle is affected as consistently as brain and peripheral nerve, and by the same process, has not been determined. Medications used in critical care units, notably sedatives and neuromuscular blocking agents, often confuse the clinical picture. The neurological pathophysiology is unknown but current evidence suggests that nervous system dysfunction arises through the same mechanisms as for systemic organs in the septic syndrome.