gebhart/patrepeval huggingface dataset:
Membrane lipid peroxidation by UV‐A: mechanism and implications (1990)

UV-A produced a dose-dependent linear increase of lipid peroxidation in liposomal membrane, as detected by the assay of (i) conjugated dienes, (ii) lipid hydroperoxides, (iii) malondialdehydes (MDA), and (iv) the fluorescent adducts formed by the reaction of MDA with glycine and also a linear dose-dependent increase of [14C]glucose efflux from the liposomes. UV-A-induced MDA production could not be inhibited by any significant degree by sodium formate, dimethyl sulfoxide, EDTA, or superoxide dismutase but was very significantly inhibited by butylated hydroxytoluene, alpha-tocopherol, sodium azide, L-histidine, dimethylfuran, and beta-carotene. MDA formation increased with an increase in the D2O content in water, leading to a maximal amount of nearly 50% enhancement of lipid peroxidation in 100% D2O vis-à-vis water used as dispersion medium. The experimental findings indicate the involvement of singlet oxygen as the initiator of the UV-A-induced lipid peroxidation.
Activation of Rac GTPase by p75 Is Necessary for c-junN-Terminal Kinase-Mediated Apoptosis (2002)

The neurotrophin receptor p75 can induce apoptosis both in vitro and in vivo. The mechanisms by which p75 induces apoptosis have remained mostly unknown. Here, we report that p75 activates Rac GTPase, which in turn activates c-jun N-terminal kinase (JNK), including an injury-specific JNK3, in an NGF-dependent manner. N17Rac blocks this JNK activation and subsequent NGF-dependent apoptosis, indicating that activation of Rac GTPase is required for JNK activation and apoptosis induced by p75. In addition, p75-mediated Rac activation is modulated by coactivation of Trk, identifying Rac GTPase as one of the key molecules whose activity is critical for cell survival and death in neurotrophin signaling. The crucial role of the JNK pathway in p75 signaling is further confirmed by the results that blocking p75 from signaling via the JNK pathway or suppressing the JNK activity itself led to inhibition of NGF-dependent death. Together, these results indicate that the apoptotic machinery of p75 comprises Rac GTPase and JNK.
Abstract 1677: CLCA2 interaction with EVA1 promotes mammary epithelial differentiation (2016)

Abstract CLCA2 is a p53-, p63-inducible transmembrane protein that is frequently downregulated in breast cancer. It is induced during differentiation of human mammary epithelial cells, and its knockdown causes epithelial-to-mesenchymal transition (EMT). To determine how CLCA2 promotes epithelial differentiation, we searched for interactors using membrane dihybrid screening. We discovered a strong interaction with the cell junctional protein EVA1 (Epithelial V-like Antigen 1) and confirmed it by co-immunoprecipitation. Like CLCA2, EVA1 is a type I transmembrane protein that is regulated by p53 and p63. It is thought to mediate homophilic cell-cell adhesion in diverse epithelial tissues. We found that EVA1 is frequently downregulated in breast tumors and breast cancer cell lines, especially those of mesenchymal phenotype. Moreover, knockdown of EVA1 in immortalized HMEC caused EMT, implying that EVA1 is essential for epithelial differentiation. Both EVA1 and CLCA2 co-localized with E-cadherin at cell-cell junctions. The interacting domains were delimited by deletion analysis, revealing the site of interaction to be the transmembrane segment (TMS). The TMS primary sequence of CLCA2 was found to be conserved throughout mammals. Moreover, competitive inhibition of the interaction by ectopic expression of the TMS caused partial EMT, suggesting that the interaction is important for differentiation. A screen for other junctional interactors revealed that CLCA2 was involved in two different complexes, one with EVA1 and ZO-1, the other with beta catenin. Overexpression of CLCA2 caused downregulation of beta catenin and beta catenin-activated genes. Thus, CLCA2 links a junctional adhesion molecule to cytosolic signaling proteins that modulate proliferation and differentiation. These results may explain how attenuation of CLCA2 causes EMT and why CLCA2 and EVA1 are frequently downregulated in metastatic breast cancer cell lines. Citation Format: Grace N.T. Ramena, Yufang Yin, Yang Yu, Vijay Walia, Randolph C. Elble. CLCA2 interaction with EVA1 promotes mammary epithelial differentiation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1677.
Journal of Clinical Pathology on the move (2002)

New look, new contents, new electronic submission and review!

Design for journals as for the fashion industry is an essential requisite, needing ongoing change.1 The emphasis is to make our journals more visually interesting and accessible to readers. So, we hope you approve of the new design and layout, both outside and in.

The cover changes will be immediately obvious and we hope popular. Internal changes affect the format of papers. They include the introduction of summary boxes, which authors will be encouraged to supply and use liberally. Editorials and commentaries have shorter snappy titles with greater detail given in subtitles. Reviews will have short abstracts or summary paragraphs, enabling them to appear in Medline. Technical changes involve the inclusion of banners, the provision of boxing and shading for tables, and the production of abbreviation lists on the first page of articles, giving the definitions of terms used.

A major development for the journals in December 2000 was to …
Three Dimensional Pharmacophore Modeling of Human CYP17 Inhibitors. Potential Agents for Prostate Cancer Therapy (2003)

We report here a molecular modeling investigation of steroidal and nonsteroidal inhibitors of human cytochrome P450 17alpha-hydroxylase-17,20-lyase (CYP17). Using the pharmacophore perception technique, we have generated common-feature pharmacophore model(s) to explain the putative binding requirements for two classes of human CYP17 inhibitors. Common chemical features in the steroid and nonsteroid human CYP17 enzyme inhibitors, as deduced by the Catalyst/HipHop program, are one to two hydrogen bond acceptors (HBAs) and three hydrophobic groups. For azole-steroidal ligands, the 3beta-OH group of ring A and the N-3 of the azole ring attached to ring D at C-17 act as hydrogen bond acceptors. A model that permits hydrogen bond interaction between the azole functionality on ring D and the enzyme is consistent with experimental deductions for type II CYP17 inhibitors where a sixth ligating atom interacts with Fe(II) of heme. In general, pharmacophore models derived for steroid and nonsteroidal compounds bear striking similarities to all azole sites mapping the HBA functionality and to three hydrophobic features describing the hydrophobic interactions between the ligands and the enzyme. Using the pharmacophore model derived for azole-steroidal inhibitors as a 3D search query against several 3D multiconformational Catalyst formatted databases, we identified several steroidal compounds with potential inhibition of this enzyme. Biological testing of some of these compounds show low to high inhibitory potency against the human CYP17 enzyme. This shows the potential of our pharmacophore model in identifying new and potent CYP17 inhibitors. Further refinement of the model is in progress with a view to identifying and optimizing new leads.
Regulation of Replicon Size in Xenopus Egg Extracts (1997)

Once a specific number of cells have been produced in the early Xenopus laevis embryo, replicon size during the S phase of the cell cycle increases. Here, it is reported that similar increase in replicon size occurred when the concentration of nuclei in replication-competent Xenopus egg extracts exceeded a critical threshold. In this system, the origin recognition complex (ORC) did not become stoichiometrically limiting for initiation, and similar amounts of this complex bound to chromatin regardless of replicon size. These data suggest that in early development, an unidentified factor controls how many preformed ORC-DNA complexes initiate DNA replication.
Efficient pilot patterns for channel estimation in OFDM systems over HF channels (1999)

In this paper, the distribution of pilot symbols in the time-frequency lattice of a multicarrier system for HF communications has been analysed. The pilot density of an OFDM modem based on the HFDL standard can be reduced, so the data rate can be about 3600 bit/s. An hexagonal pilot pattern has been proposed and compared with rectangular geometries. Hexagonal distribution of the pilots is optimum in terms of sampling efficiency and it provides better performance in terms of BER.
CONSeQuence: Prediction of Reference Peptides for Absolute Quantitative Proteomics Using Consensus Machine Learning Approaches (2011)

Mass spectrometric based methods for absolute quantification of proteins, such as QconCAT, rely on internal standards of stable-isotope labeled reference peptides, or "Q-peptides," to act as surrogates. Key to the success of this and related methods for absolute protein quantification (such as AQUA) is selection of the Q-peptide. Here we describe a novel method, CONSeQuence (consensus predictor for Q-peptide sequence), based on four different machine learning approaches for Q-peptide selection. CONSeQuence demonstrates improved performance over existing methods for optimal Q-peptide selection in the absence of prior experimental information, as validated using two independent test sets derived from yeast. Furthermore, we examine the physicochemical parameters associated with good peptide surrogates, and demonstrate that in addition to charge and hydrophobicity, peptide secondary structure plays a significant role in determining peptide "detectability" in liquid chromatography-electrospray ionization experiments. We relate peptide properties to protein tertiary structure, demonstrating a counterintuitive preference for buried status for frequently detected peptides. Finally, we demonstrate the improved efficacy of the general approach by applying a predictor trained on yeast data to sets of proteotypic peptides from two additional species taken from an existing peptide identification repository.
The local immune response to large bowel tumors. (1985)

Methods are described for the purification on isokinetic gradients of isolated large bowel lamina propria lymphocytes (LPL) and large bowel adenocarcinoma-infiltrating lymphocytes (TIL). The in vitro cytotoxic and proliferative responses of these lymphocytes and of peripheral blood lymphocytes from tumor patients were assayed. Neither K cell nor NK cell cytotoxic activity was detected in LPL and TIL, although both types of lytic response were present in PBL. Lectin-induced cytotoxicity was mediated by LPL and TIL populations, but their responses in this assay were reduced comparable to that of PBL. Although TIL comprised equivalent T cell proportions to PBL, the proliferative response of TIL T cells was comparatively lower. LPL and TIL populations, but their responses in this assay were reduced comparable to that of PBL. Although TIL comprised equivalent T cell proportions to PBL, the proliferative response of TIL T cells was comparatively lower. Co-culture experiments and attempts to induce suppressor cells with concanavalin A suggested that the reduced proliferative response of T cells infiltrating these tumors was not due to the action of suppressor lymphocytes.
“Pathogen-Mimicking” Nanoparticles for Vaccine Delivery to Dendritic Cells (2007)

A clinically relevant delivery system that can efficiently target and deliver antigens and adjuvant to dendritic cells (DCs) is under active investigation. Immunization with antigens and immunomodulators encapsulated in poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles elicits potent cellular immune responses; but understanding how this mode of delivery affects DCs and priming of naive T cells needs further investigation. In the current study, we assessed the extent of maturation of DCs after treatment with monophosphoryl lipid A (MPLA) encapsulated in PLGA nanoparticles and the generation of primary T-cell immune responses elicited by DCs loaded with antigens using this approach. Results indicated that DCs up-regulated the expression of surface maturation markers and demonstrated an enhanced allostimulatory capacity after treatment with MPLA containing PLGA nanoparticles. Treatment of DCs with MPLA containing nanoparticles released high amounts of proinflammatory and TH1 (T helper 1) polarizing cytokines and chemokines greater than that achieved by MPLA in solution. The delivery of ovalbumin in PLGA nanoparticles to DCs induced potent in vitro and in vivo antigen-specific primary TH1 immune responses that were furthermore enhanced with codelivery of MPLA along with the antigen in the nanoparticle formulation. Delivery of MUC1 lipopeptide (BLP25, a cancer vaccine candidate) and MPLA in PLGA nanoparticles to human DCs induced proliferation of MUC1 reactive T cells in vitro demonstrating the break in tolerance to self-antigen MUC1. These results demonstrated that targeting antigens along with toll-like receptor ligands in PLGA nanoparticles to DCs is a promising approach for generating potent TH1 polarizing immune responses that can potentially override self-tolerance mechanisms and become beneficial in the immunotherapy of cancer and infectious diseases.
Levamisole and inorganic pyrophosphate inhibit beta-glycerophosphate induced mineralization of bone formed in vitro. (1987)

The addition of the organic phosphate, beta-glycerophosphate, to the culture media of osteoid forming cells or tissues will induce formation of mineralized bone. The mechanisms behind this phenomenon are not clearly understood. In order to gain new understanding of organic phosphate induced mineralization of bone it was decided to attempt to inhibit this process in two fundamentally different ways. Firstly, the reversible inhibitor of alkaline phosphatase, Levamisole, was used to help define the role of alkaline phosphatase in mineralization in vitro. Secondly, inorganic pyrophosphate, a known inhibitor of hydroxyapatite (HA) formation was also used. It was hypothesized that inorganic pyrophosphate, in addition to its ability to block HA formation, might also interfere with organic phosphate access to alkaline phosphatase and thereby prevent mineralization. The data show that mineralization is blocked when alkaline phosphatase activity is inhibited by Levamisole prior to but not after osteoid maturation. Inorganic pyrophosphate blocks organic phosphate induced mineralization whether added before or after osteoid formation. Organic phosphate effects on alkaline phosphatase activity are reversed by the addition of inorganic pyrophosphate either before or after osteoid formation. These findings suggest a role for alkaline phosphatase in organic phosphate induced mineralization. The data show further that inorganic pyrophosphate may effect mineralization of bone not only by blocking apatite formation but possibly by modulating organic phosphate metabolism.
Modification and evaluation of a multichannel blood cell counting system for blood analysis in veterinary hematology. (1987)

A multichannel, semiautomated, blood cell counting system (Coulter Counter Model S550) was modified for use in veterinary hematology by increasing both the erythrocyte and leukocyte aperture currents to 225 V and 195 V, respectively, followed by calibration with human blood. It was evaluated by use of 350 samples from dogs, cats, horses, and cows. Values for leukocyte count, erythrocyte count, mean corpuscular volume, and hematocrit generated by the S550 were compared with values generated by an automated multichannel counter with histogram capability and other reference procedures when appropriate. Mean differences for values between S550 and reference values were less than calibration tolerance limits for the instrument. Correlation coefficients were excellent for all values of each species. To assess behavior of leukocytes of the different species with respect to the counting threshold, leukocyte size distribution histograms were generated for all samples analyzed on the S550. Means for mean leukocyte volumes in diluent and lysing reagents were 55.5, 56.6, 67.4, and 72.8 fl for dogs, cats, horses, and cows, respectively. Canine leukocyte counts, because of small leukocyte size, were an average of 14% less for 5 samples analyzed on the unmodified instrument, compared with analysis after increasing the leukocyte aperture current. Leukocyte threshold failures attributable to interfering particles, resulting in falsely high counts, were recognized in 14%, 10%, 8% and 0% of feline, bovine, canine, and equine samples, respectively. The magnitude of error in these samples averaged 5% for cows and dogs, but was considered not important. However, leukocyte counts of feline samples in this group averaged 44% falsely high.
Structure-Activity Relationships for the Inhibition of Plasmin and Plasminogen Activation by Aromatic Diamidines and a Study of the Effect of Plasma Proteins on the Inhibition Process (1973)

Summary 1. Structure-activity relationships for the inhibition of human plasmin were established for a large series of aromatic diamidines. The compounds are reversible competitive inhibitors and block the amidase and fibrinolytic activities of the enzym. The results confirm pentamidine (4,4’-diamidino α ω-diphenoxy-pentane) as the leading inhibitor (Ki = 3.3 (μM) and show distinct differences in the inhibitory spectrum of diamidines against plasmin as compared with trypsin, pancreatic kallikrein and thrombin. 2. Diamidines are potent inhibitors of the SK-dependent activation of human plasminogen and of the activation of bovine plasminogen by the SK-human plasmin activator complex. Pentamidine is again the most powerful inhibitor of these systems. 3. In fibrinolytic assays of plasmin and in plasminogen activation tests the relative strength of diamidines as compared with E-ACA is greatly influenced by the test conditions. The decisive factor is the presence in the incubation mixtures of lesser or greater amounts of plasma or serum proteins which bring about a fall in the absolute strength of diamidines and an increase in the absolute strength of E-ACA. In the fibrinolytic assay of plasmin, this modifying effect of added serum is based on a time- dependent interaction with the enzyme, thereby presumably altering its susceptibility to inhibition.
CXCR4: chemokine receptor extraordinaire (2000)

Current investigations show that chemokine receptor CXCR4 is functionally expressed on a multitude of tissues and cell types, including different leukocyte subsets, hematopoietic progenitor cells and non-hematopoietic cells such as endothelial and epithelial cells. In 1996 CXCR4 was discovered as one of the co-factors required for supporting T-lymphocyte tropic HIV infection into permissive cells and, as a consequence, much attention has been paid to this receptor in terms of HIV pathophysiology. The sudden surge of interest and subsequent growth in CXCR4 research following this discovery has led to a number of surprising findings. As well as being important for lymphocyte trafficking and recruitment at sites of inflammation, it appears that CXCR4 and its ligand stromal cell-derived factor-1 play an important role in hematopoiesis and developmental processes such as organogenesis, vascularization and embryogenesis. These findings provide new insight into the activities of chemokine receptors on both hematopoietic and non-hematopoietic cells and indicate that these molecules have both a more widespread cellular expression pattern and a wider biological role than first envisaged.
Novel Monoamine Oxidase Inhibitors, 3-(2-Aminoethoxy)-1,2-benzisoxazole Derivatives, and Their Differential Reversibility (2002)

Although possible usefulness of non-selective monoamine oxidase (MAO) inhibitors for Parkinson's disease therapy has been suggested in the literature, MAO inhibitors whose inhibition is reversible and have dual action to both MAO-A and -B subtypes is not available yet. Subtype selectivity and reversibility of a series of novel MAO inhibitors, 3-(2-aminoethoxy)-1,2-benzisoxazole derivatives, were studied. Several dual MAO inhibitors, which inhibit both MAO-A and -B, were obtained. When administered to mice, their effects were generally reversible. Among the derivatives, RS-1636 and RS-1653 had much longer duration of brain MAO-B inhibition than that of MAO-A. In vitro, the inhibited MAO-A activity by these compounds was partially recovered by buffer change at 4 degrees C, while little MAO-B activity was recovered. Although it is not fully elucidated yet, the reversibility of these inhibitors is probably determined primarily by this dissociation profile. This unique differential reversibility indicates that optimization of the balance of actions can be achieved by differentiating reversibility to each target molecule.
Type 1 Diabetic Serum Interferes with Pancreatic β-cell Ca2+ -Handling (2007)

The aim of this study was to clarify the frequency of patients with type 1 diabetes that have serum that increases pancreatic beta-cell cytoplasmic free Ca(2+) concentration, [Ca(2+)](i), and if such an effect is also present in serum from first-degree relatives. We also studied a possible link between the serum effect and ethnic background as well as presence of autoantibodies. Sera obtained from three different countries were investigated as follows: 82 Swedish Caucasians with newly diagnosed type 1 diabetes, 56 Americans with different duration of type 1 diabetes, 117 American first-degree relatives of type 1 diabetic patients with a mixed ethnic background and 31 Caucasian Finnish children with newly diagnosed type 1 diabetes. Changes in [Ca(2+)](i) , upon depolarization, were measured in beta-cells incubated overnight with sera from type 1 diabetic patients, first-degree relatives or healthy controls. Our data show that there is a group constituting approximately 30% of type 1 diabetic patients of different gender, age, ethnic background and duration of the disease, as well as first-degree relatives of type 1 diabetic patients, that have sera that interfere with pancreatic beta-cell Ca(2+)-handling. This effect on beta-cell [Ca(2+)](i) could not be correlated to the presence of autoantibodies. In a defined subgroup of patients with type 1 diabetes and first-degree relatives a defect Ca(2+)-handling may aggravate development of beta-cell destruction.
Applications of micromechatronics in minimally invasive surgery (1998)

Many surgical procedures are now performed using the techniques of minimally invasive surgery (MIS), in which unnecessary trauma is limited by reducing the size of incisions to less than about 1 cm or by using catheters or endoscopes threaded through vessels, the gastrointestinal tract, or other tubular structures. Micromechatronic technologies have great potential to allow access to regions now inaccessible, or to enhance the surgeon's abilities in applications where current minimally invasive techniques do not permit the full range of human dexterity and perception. Key needs and applications in MIS are identified, and relevant technologies, methods, and systems issues in mechatronics are discussed. The authors' millirobotic system for MIS of the abdomen is used as an example.