gebhart/patrepeval huggingface dataset:
Inactivation of the small GTP binding protein Rho induces multinucleate cell formation and apoptosis in murine T lymphoma EL4 (1996)

The small G-protein Rho regulates the actin microfilament-dependent cytoskeleton. Exoenzyme C3 of Clostridium botulinum ADP-ribosylates Rho at Asn41, a modification that functionally inactivates Rho. Using a Sindbis virus-based transient gene expression system, we studied the role of Rho in murine EL4 T lymphoma cells. We generated a double subgenomic infectious Sindbis virus (dsSIN:C3) recombinant which expressed C3 in >95% of EL4 cells. This intracellular C3 resulted in modification and inactivation of virtually all endogenous Rho. dsSIN:C3 infection led to the formation of multinucleate cells, likely by inhibiting the actin microfilament-dependent step of cytokinesis. Intriguingly, in spite of the inhibition of cytokinesis, karyokinesis continued, with the result that cells containing a nuclear DNA content as high as 16N (eight nuclei) were observed. In addition, dsSIN:C3-mediated inactivation of Rho was a potent activator of apoptosis in EL4 cells. To discern whether the formation of multinucleate cells was responsible for the activation of apoptosis, 5-fluorouracil (5-FUra) was used to induce cell cycle arrest. As expected, EL4 cells treated with 5-FUra were prevented from forming multinucleate cells upon infection with dsSIN:C3. dsSIN:C3 infection, however, still caused marked apoptosis in 5-FUra-treated cells, indicating that this activation of apoptosis was independent of multinucleate cell formation.
Medical image registration: a review (2012)

This paper presents a review of automated image registration methodologies that have been used in the medical field. The aim of this paper is to be an introduction to the field, provide knowledge on the work that has been developed and to be a suitable reference for those who are looking for registration methods for a specific application. The registration methodologies under review are classified into intensity or feature based. The main steps of these methodologies, the common geometric transformations, the similarity measures and accuracy assessment techniques are introduced and described.
Extensin: repetitive motifs, functional sites, post‐translational codes, and phylogeny (1994)

Homologous hydroxyproline-rich glycoproteins (HRGPs) of the plant extracellular matrix include extensins, repetitive proline-rich proteins (RPRPs), some nodulins, gum arabic glycoprotein (GAGP), arabinogalactan-proteins (AGPs), and chimeric proteins such as potato lectin which contain an extensin module fused to a lectin. The key to the role of HRGPs in cell wall self-assembly and cell extension lies in their chemistry, which is dependent on extensive post-translational modifications (PTMs): hydroxylation, glycosylation, and cross-linking. Repetitive peptide motifs characterize HRGPs. One or more repetitive peptide motifs and their variants, singly or in combination, may constitute functional sites involved in various aspects of cell wall assembly, as follows: (i) X-Hypn including Ser-Hyp4 (arabinosylation site, molecular rigidity, and reptation). (ii) Pro-Hyp-Val-Tyr-Lys and variants (putative intermolecular cross-links, adhesion, cohesion, and possible beta-turns). (iii) Tyr-X-Tyr-Lys (intramolecular isodityrosine [IDT] cross-links increase molecular rigidity and hydrophobicity). (iv) (Glyco)peptide palindromes (centrosymmetric domains: putative self-assembly nucleation sites). (v) Ionic interaction sites (protein-protein and protein-carbohydrate cross-links). (vi) Hyp and Ser glycosylation sites (enhance conformational stability and molecular recognition). (vii) Extensin modules in chimeric proteins (e.g. solanaceous lectins). Rules for the post-translational modifications are emerging: (i) Hydroxylation of proline residues may depend on multiple, sequence-specific prolyl hydroxylases rather than on a single (polyproline-II) conformation-dependent enzyme. Furthermore, Lys-Pro, Tyr-Pro, and Phe-Pro are not hydroxylated, while Pro-Val is always. (ii) Contiguity of Hyp residues probably determines the extent of Hyp glycosylation, blocks of tetrahydroxyproline (Hyp4) being the most highly arabinosylated, while single non-contiguous Hyp residues are rarely arabinosylated, although they are likely attachment sites for the larger arabinogalactan substituents of gum arabic glycoprotein and arabinogalactan-proteins. (iii) While intramolecular cross-links involve IDT, unidentified intermolecular cross-links most likely involve the Val-Tyr-Lys motif (perhaps also Val-Lys-Pro-Tyr-His-Pro), probably as an adduct between Tyr and Lys catalyzed in vitro by a pI 4.6 extensin cross-linking peroxidase. Thus, we can classify HRGPs functionally as either cross-linking or non-cross-linking, i.e. CL- or NCL-extensins. Their protistan origin obscures the phylogenetic affinities of a single extensin-HRGP family due to their sequence divergence. We propose a phylogenetic series ranging from the minimally glycosylated basic RPRPs to the highly glycosylated acidic AGPs. Furthermore, based on similarities between dicots and gymnosperm extensins, and their marked difference from graminaceous monocot extensins, graminaceous monocot and dicot lines may have diverged as early as the progymnosperms.(ABSTRACT TRUNCATED AT 400 WORDS)
Monoclonal antibody therapy in rheumatoid arthritis (1998)

Monoclonal antibodies bind to their targets with high specificity and therefore have excellent potential as therapeutic agents. Biotechnological advances have allowed the production of large quantities of engineered monoclonal antibodies for therapeutic use. Recent research in rheumatoid arthritis has identified important mediators of synovitis. Monoclonal antibodies targeting these have been tested in clinical trials over the last decade. Anti-cytokine therapies, in particular anti-tumour necrosis factor alpha monoclonal antibodies, suppressed inflammation and produced rapid symptomatic improvement. Anti-lymphocyte monoclonal antibodies produced long-lasting disease suppression in animal models of rheumatoid arthritis. The use of depleting anti-lymphocyte monoclonal antibodies in rheumatoid arthritis had been disappointing as they did not penetrate the synovial joint in sufficient quantity to suppress disease without producing severe and protracted peripheral blood lymphopenia. Consequently, their use in rheumatoid arthritis had been abandoned. In contrast, clinical trials of non-depleting anti-CD4 monoclonal antibodies in rheumatoid arthritis showed that they could suppress synovitis. However, it remains unclear whether they could lead to prolonged disease improvement.
Effect of timing of dosing in relation to food intake on the pharmacokinetics of esomeprazole (2007)

Esomeprazole bioavailability was reduced when taken within 15 min before eating a high-fat meal vs. that while fasting.
Tight Integration of New 5G Air Interface and LTE to Fulfill 5G Requirements (2015)

Integration of new radio technologies to legacy ones has always been an important feature in any wireless communication generation shift and it is envisioned that for the transition to 5G this will be even more critical. Different 5G research projects have acknowledged the demand for a new air interface that will be designed to operate in higher frequency bands (compared to the ones currently allocated to LTE) where propagation is more challenging and coverage is spotty. This paper proposes a radio access network (RAN) architecture that realizes a tight integration of this new air interface with LTE to enable cross-air interface optimizations such as common resource management, faster mobility and simultaneous multi-connectivity features. The tight integration also aims at leveraging both the better coverage of LTE and the higher capacity of the higher frequency bands. In order to realize this integration, a common protocol layer (also called integration layer) lying on the top of lower layer protocols specified per air interface is proposed. The paper analyzes the alternatives for this integration layer, having the LTE protocol stack specified by 3GPP as a reference model. A recommendation is issued and, based on that, potential multi-connectivity features are presented.
Partial Hydrolysis of Poly(2‐ethyl‐2‐oxazoline) and Potential Implications for Biomedical Applications? (2012)

The hydrolysis of PEtOx is studied to evaluate the potential toxicity of partially hydrolyzed polymers that might interfere with its increasing popularity for biomedical applications. The hydrolysis of PEtOx is studied in the presence of digestive enzymes (gastric and intestinal) and at 5.8 M hydrochloric acid as a function of temperature (57, 73, 90, and 100 °C). It is found that PEtOx undergoes negligible hydrolysis at 37 °C and that thermal and solution properties are not altered when up to 10% of the polymer backbone is hydrolyzed. Mucosal irritation and cytotoxicity is also absent up to 10% hydrolysis levels. In conclusion, PEtOx will not decompose at physiological conditions, and partial hydrolysis will not limit its biomedical applications.
Characterization of Glycosylation Sites of the Epidermal Growth Factor Receptor (2003)

The epidermal growth factor receptor is a transmembrane glycoprotein that mediates the cellular responses to epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). In this study of the human EGF receptor naturally expressed in A431 cells, the glycosylation sites of the full-length, membrane-bound receptor and of a secreted form of the receptor were characterized by mass spectrometry. Our data show that the naturally expressed human EGF receptor is fully glycosylated on eight of the 11 canonical sites; two of the sites are not glycosylated, and one is partially glycosylated, a pattern of site-usage similar but not identical to those reported for the recombinant human EGF receptor heterologously expressed in Chinese hamster ovary cells. We also confirm the partial glycosylation of an atypical NNC site first identified in the receptor expressed in Chinese hamster ovary cells. We show that an additional canonical site in the secreted form of the receptor is fully glycosylated. While the pattern of glycosylation is the same for the sites shared by the full-length and the secreted forms of the receptor, the oligosaccharides of the full-length receptor are more extensively processed. Finally, we provide evidence that in addition to the known secreted form of the receptor, a proteolytic cleavage product of the receptor corresponding to the full extracytoplasmic, ligand-binding domain is present in the conditioned medium.
Phenotypic and functional analysis of T-cell precursors in the human fetal liver and thymus: CD7 expression in the early stages of T- and myeloid-cell development (1993)

It has been proposed that the CD7 molecule is the first antigen expressed on the membrane of cells committed to the T-cell lineage during human fetal T-cell ontogeny. To further identify the pre-T cell subpopulation that migrates to the thymus early in ontogeny, we analyzed the phenotypic and functional characteristics of the fetal liver populations separated on the basis of CD7 expression. Three populations expressing different levels of CD7 were observed: CD7bright, CD7dull, and CD7-. A CD7bright population depleted of mature T, B, and myeloid cells (lineage negative, lin-) and mostly composed of CD56+ CD34- natural killer cells did not mature into T cells in a fetal thymic organ culture (FTOC) assay and was devoid of myeloid progenitors in a clonal colony-forming cell assay. In contrast, the CD7-/dull CD34+ lin- populations were capable of differentiating into phenotypically mature T cells after injection into FTOC and contained early myeloid progenitors. Here we phenotypically compared the fetal liver CD7 populations with the most immature fetal thymic subset that differentiated in the FTOC assay, namely the triple negative (TN, CD3- CD4-CD8-) thymocytes. Fetal TN lin- expressed high levels of CD34 marker and were further subdivided by their expression of CD1 antigen, because CD1- TN thymocytes express higher levels of CD34 antigen compared with CD1+ TN cells. CD1- lin -TN thymocytes are characterized by expressing high levels of CD2, CD7, and CD34 markers and dull levels of CD5, CD10, and CD28 molecules. We could not find fetal liver pre-T cells with a phenotype equivalent to that of TN thymocytes. Our data show that CD7 does not necessarily identify T-cell precursors during fetal T-cell development and strongly support the hypothesis that the acquisition of early T-cell markers as CD2, CD28, and CD5 molecules on the cell surface of T-cell progenitors takes place intrathymically.
Vulnerability of Pathogenic Biofilms to Micavibrio aeruginosavorus (2006)

The host specificity of the gram-negative exoparasitic predatory bacterium Micavibrio aeruginosavorus was examined. M. aeruginosavorus preyed on Pseudomonas aeruginosa, as previously reported, as well as Burkholderia cepacia, Klebsiella pneumoniae, and numerous clinical isolates of these species. In a static assay, a reduction in biofilm biomass was observed as early as 3 hours after exposure to M. aeruginosavorus, and an approximately 100-fold reduction in biofilm cell viability was detected following a 24-h exposure to the predator. We observed that an initial titer of Micavibrio as low as 10 PFU/well or a time of exposure to the predator as short as 30 min was sufficient to reduce a P. aeruginosa biofilm. The ability of Micavibrio to reduce an existing biofilm was confirmed by scanning electron microscopy. In static and flow cell experiments, M. aeruginosavorus was able to modify the overall P. aeruginosa biofilm structure and markedly decreased the viability of P. aeruginosa. The altered biofilm structure was likely caused by an increase in cell-cell interactions brought about by the presence of the predator or active predation. We also conducted a screen to identify genes important for P. aeruginosa-Micavibrio interaction, but no candidates were isolated among the approximately 10,000 mutants tested.
Acetyl-CoA carboxylase-a as a novel target for cancer therapy (2009)

Acetyl-CoA carboxylases (ACC) are rate-limiting enzymes in de novo fatty acid synthesis, catalyzing ATP-dependent carboxylation of acetyl-CoA to form malonyl-CoA. Malonyl-CoA is a critical bi-functional molecule, i.e., a substrate of fatty acid synthase (FAS) for acyl chain elongation (fatty acid synthesis) and an inhibitor of carnitine palmitoyltransferase I (CPT-I) for fatty acid beta-oxidation. Two ACC isoforms have been identified in mammals, i.e. ACC-alpha (ACCA, also termed ACC1) and ACC-beta (ACCB, also designated ACC2). ACC has long been used as a target for the management of metabolic diseases, such as obesity and metabolic syndrome, and various inhibitors have been developed in clinical trials. Recently, ACCA up-regulation has been recognized in multiple human cancers, promoting lipogenesis to meet the need of cancer cells for rapid growth and proliferation. Therefore, ACCA might be effective as a potent target for cancer intervention, and the inhibitors developed for the treatment of metabolic diseases would be potential therapeutic agents for cancer therapy. This review summarizes our recent findings and updates the current understanding of the ACCA with focus on cancer research.
Physical Unclonable Functions: A Primer (2014)

Physical unclonable functions (PUFs) make use of the measurable intrinsic randomness of physical systems to establish signatures for those systems. PUFs provide a means to generate unique keys that don't need to be stored in nonvolatile memory, and they offer exciting opportunities for new authentication and supply chain security technologies.
Enhanced Delivery of SN-38 to Human Tumor Xenografts with an Anti-Trop-2–SN-38 Antibody Conjugate (Sacituzumab Govitecan) (2015)

These studies confirm a superior SN-38 tumor delivery by IMMU-132 compared with irinotecan.
Extrahypothalamic Growth-Hormone-Releasing Factor (GRF) Secretion Is a Rare Cause of Acromegaly: Plasma GRF Levels in 177 Acromegalic Patients* (1984)

To assess the frequency with which acromegaly is caused by ectopic secretion of GRF, we collected plasma samples from 177 unselected acromegalic patients. The samples together with those of three acromegalic patients with previously diagnosed tumors secreting GRF and of normal subjects were assayed in 3 independent GRF RIAs. Plasma immunoreactive GRF (IR-GRF) levels in normal subjects were either undetectable or detectable at levels up to 62.5 pg/ml. In none of the 177 specimens from acromegalic patients were IR-GRF values detectable in all assays, and in the most sensitive assay, the levels were similar to those in normal subjects, with the highest level measuring 82 pg/ml. In contrast, plasma IR-GRF found in the 3 patients with tumors that secreted GRF ranged from 2.0-24.4 ng/ml. These data suggest that extrahypothalamic GRF secretion is a rare cause of acromegaly. However, it is important that this rare cause of acromegaly be diagnosed before the patient has unnecessary surgery and/or irradiation directed at the pituitary. We recommend that plasma IR-GRF be measured in each new acromegalic patient.
Retinoid X receptor alpha forms tetramers in solution. (1995)

Protein-protein interactions allow the retinoid X receptor (RXR) to bind to cognate DNA as a homo- or a heterodimer and to participate in mediating the effects of a variety of hormones on gene transcription. Here we report a systematic study of the oligomeric state of RXR in the absence of a DNA template. We have used electrophoresis under nondenaturing conditions and chemical crosslinking to show that in solution, RXR alpha forms homodimers as well as homotetramers. The dissociation constants governing dimer and tetramer formation were estimated by fluorescence anisotropy studies. The results indicate that RXR tetramers are formed with a high affinity and that at protein concentrations higher than about 70 nM, tetramers will constitute the predominant species. Tetramer formation may provide an additional level of the regulation of gene transcription mediated by RXRs.
Line of Sight and Alternative Representations of Aberrations of the Eye (2000)

Several methods for representing pupil plane aberrations based on wavefront height, slope, and curvature are discussed. The choice of reference axis and reference surface is shown to strongly affect the appearance of the representation. Special attention will be paid to the use of the line of sight (the line from the fixation point to the center of the pupil) as the reference axis. We show that the line of sight is ambiguous and does not determine the amount of prism in the wavefront.
Fractal antenna engineering: the theory and design of fractal antenna arrays (1999)

A fractal is a recursively generated object having a fractional dimension. Many objects, including antennas, can be designed using the recursive nature of a fractal. In this article, we provide a comprehensive overview of recent developments in the field of fractal antenna engineering, with particular emphasis placed on the theory and design of fractal arrays. We introduce some important properties of fractal arrays, including the frequency-independent multi-band characteristics, schemes for realizing low-sidelobe designs, systematic approaches to thinning, and the ability to develop rapid beam-forming algorithms by exploiting the recursive nature of fractals. These arrays have fractional dimensions that are found from the generating subarray used to recursively create the fractal array. Our research is in its infancy, but the results so far are intriguing, and may have future practical applications.
High-capacitance Cu/Ta/sub 2/O/sub 5//Cu MIM structure for SoC applications featuring a single-mask add-on process (2003)

This paper presents a metal-insulator-metal capacitor for SoC applications which has the highest capacitance density (up to 12 fF//spl mu/m/sup 2/) ever reported for a device in this field. The simple MIM structure allowed development of the process as a single-mask add-on to conventional Cu BEOL processing.
Normal-Range Blood Lactate Concentration in Septic Shock Is Prognostic and Predictive (2012)

We hypothesized that lactate levels even within the normal range are prognostic and that low lactate levels predict a beneficial response to vasopressin infusion in septic shock. We conducted a retrospective analysis using the Vasopressin in Septic Shock Trial (VASST) as a derivation cohort (n = 665), then validated using another single-center septic shock cohort, St Paul's Hospital (SPH) cohort (n = 469). Lactate levels were divided into quartiles. The primary outcome variable was 28-day mortality in both cohorts. We used receiver operating characteristic (ROC) curve analysis to compare the prognostic value of lactate concentrations versus Acute Physiology and Chronic Health Evaluation II scores. We then explored whether lactate concentrations might predict beneficial response to vasopressin compared with noradrenaline in VASST. Normal lactate range is less than 2.3 mmol/L. At enrollment, patients in the second quartile (1.4 < lactate < 2.3 mmol/L) had significantly increased mortality and organ dysfunction compared with patients who had lactate ≤ 1.4 mmol/L (quartile 1) (P < 0.0001). Quartile 2 outcomes were as severe as quartile 3 (2.3 ≤ lactate < 4.4 mmol/L) outcomes. Baseline lactate values (ar ea under the ROC curve = 0.63, 0.66; VASST, SPH) were as good as Acute Physiology and Chronic Health Evaluation II scores (area under the ROC curve = 0.66, 0.73; VASST, SPH) as prognostic indicators of 28-day mortality. Lactate concentrations of 1.4 mmol/L or less predicted a beneficial response in those randomized to vasopressin compared with noradrenaline in VASST (P < 0.05). Lactate concentrations within the "normal" range can be a useful prognostic indicator in septic shock. Furthermore, patients whose lactate level is less than or equal to 1.4 mmol/L may benefit from vasopressin infusion.
Vascular Endothelial Growth Factor and Its Receptors Expression in the Rat Eye. (2001)

Vascular endothelial growth factor (VEGF) plays a pivotal role in the angiogenesis of embryonic development and tumorigenesis. Recent extensive studies show that VEGF also affects non-vascular cells. In the present study, we performed an immunohistochemical examination of cellular distribution of VEGF and its receptors, Flt-1 and Flk-1, in the retina in vivo and in vitro. Moreover, we addressed their expression in the cornea, iris and ciliary body. In the retina, both Flt-1 and Flk-1 were localized to the axon of retinal ganglion cells (RGCs) and to the retinal pigment epithelium. In vitro experiments showed that both VEGF receptors seemed to be expressed in the cytoplasm of RGCs and Müller cells. In the extra-ocular tissues, ciliary body epithelium showed VEGF, Flt-1 and Flk-1 expression, while iris epithelium showed VEGF and Flk-1 but not Flt-1. Corneal endothelium only showed Flk-1. These data support the hypothesis that VEGF plays a role in many ocular tissues via Flt-1, Flk-1 or both.