gebhart/patrepeval huggingface dataset:
Requirement for diacylglycerol and protein kinase C in HeLa cell-substratum adhesion and their feedback amplification of arachidonic acid production for optimum cell spreading. (1993)

Release of arachidonic acid (AA) and subsequent formation of a lipoxygenase (LOX) metabolite(s) is an obligatory signal to induce spreading of HeLa cells on a gelatin substratum (Chun and Jacobson, 1992). This study characterizes signaling pathways that follow the LOX metabolite(s) formation. Levels of diacylglycerol (DG) increase upon attachment and before cell spreading on a gelatin substratum. DG production and cell spreading are insignificant when phospholipase A2 (PLA2) or LOX is blocked. In contrast, when cells in suspension where PLA2 activity is not stimulated are treated with exogenous AA, DG production is turned on, and inhibition of LOX turns it off. This indicates that the formation of a LOX metabolite(s) from AA released during cell attachment induces the production of DG. Consistent with the DG production is the activation of protein kinase C (PKC) which, as with AA and DG, occurs upon attachment and before cell spreading. Inhibition of AA release and subsequent DG production blocks both PKC activation and cell spreading. Cell spreading is also blocked by the inhibition of PKC with calphostin C or sphingosine. The inhibition of cell spreading induced by blocking AA release is reversed by the direct activation of PKC with phorbol ester. However, the inhibition of cell spreading induced by PKC inhibition is not reversed by exogenously applied AA. In addition, inhibition of PKC does not block AA release and DG production. The data indicate that there is a sequence of events triggered by HeLa cell attachment to a gelatin substratum that leads to the initiation of cell spreading: AA release, a LOX metabolite(s) formation, DG production, and PKC activation. The data also provide evidence indicating that HeLa cell spreading is a cyclic feedback amplification process centered on the production of AA, which is the first messenger produced in the sequence of messengers initiating cell spreading. Both DG and PKC activity that are increased during HeLa cell attachment to a gelatin substratum appear to be involved. DG not only activates PKC, which is essential for cell spreading, but is also hydrolyzed to AA. PKC, which is initially activated as consequence of AA production, also increases more AA production by activating PLA2.
A fluorescence stopped‐flow kinetic study of the conformational activation of α‐chymotrypsin and several mutants (2004)

The kinetic activation parameters (activation free energy, activation free enthalpy, and activation free entropy change) of the conformational change of alpha-chymotrypsin from an inactive to the active conformation were determined after a pH jump from pH 11.0 to pH 6.8 by the fluorescence stopped-flow method. The conformational change was followed by measuring changes in the protein fluorescence. For the bovine wild-type protein, the same kinetic parameters are obtained as in the study of proflavin binding. Several mutants were made with the goal to accelerate or decelerate this conformational transition. The inspiration for the choice of the mutants came from a previous modelling study done on the bovine wild-type chymotrypsin. The results of the fluorescence stopped flow experiments show that several mutants behaved as was expected based on the information provided by the modeling study on the wild-type variant. For some mutants our assumptions were not correct, and therefore additional modeling studies of the activation pathways of these mutant proteins are necessary to be able to explain the observed kinetic behavior.
Comparative Genomics of Regulation of Fatty Acid and Branched-Chain Amino Acid Utilization in Proteobacteria (2008)

Bacteria can use branched-chain amino acids (ILV, i.e., isoleucine, leucine, valine) and fatty acids (FAs) as sole carbon and energy sources converting ILV into acetyl-coenzyme A (CoA), propanoyl-CoA, and propionyl-CoA, respectively. In this work, we used the comparative genomic approach to identify candidate transcriptional factors and DNA motifs that control ILV and FA utilization pathways in proteobacteria. The metabolic regulons were characterized based on the identification and comparison of candidate transcription factor binding sites in groups of phylogenetically related genomes. The reconstructed ILV/FA regulatory network demonstrates considerable variability and involves six transcriptional factors from the MerR, TetR, and GntR families binding to 11 distinct DNA motifs. The ILV degradation genes in gamma- and betaproteobacteria are regulated mainly by a novel regulator from the MerR family (e.g., LiuR in Pseudomonas aeruginosa) (40 species); in addition, the TetR-type regulator LiuQ was identified in some betaproteobacteria (eight species). Besides the core set of ILV utilization genes, the LiuR regulon in some lineages is expanded to include genes from other metabolic pathways, such as the glyoxylate shunt and glutamate synthase in Shewanella species. The FA degradation genes are controlled by four regulators including FadR in gammaproteobacteria (34 species), PsrA in gamma- and betaproteobacteria (45 species), FadP in betaproteobacteria (14 species), and LiuR orthologs in alphaproteobacteria (22 species). The remarkable variability of the regulatory systems associated with the FA degradation pathway is discussed from functional and evolutionary points of view.
Self-calibrating time-resolved near infrared spectroscopy (2019)

Time-resolved near infrared spectroscopy is considered to be a gold standard technique when measuring absolute values of tissue optical properties, as it provides separable and independent information about both tissue absorption and scattering. However, time-resolved instruments require an accurate characterization by measuring the instrument response function in order to decouple the contribution of the instrument itself from the measurement. In this work, a new approach to the methodology of analysing time-resolved data is presented where the influence of instrument response function is eliminated from the data and a self-calibrating analysis is proposed. The proposed methodology requires an instrument to provide at least two wavelengths and allows spectral parameters recovery (optical properties or constituents concentrations and reduced scatter amplitude and power). Phantom and in-vivo data from two different time-resolved systems are used to validate the accuracy of the proposed self-calibrating approach, demonstrating that parameters recovery compared to the conventional curve fitting approach is within 10% and benefits from introducing a spectral constraint to the reconstruction problem. It is shown that a multi-wavelength time-resolved data can be used for parameters recovery directly without prior calibration (instrument response function measurement).
Reversal of potassium channel deficiency in cells from failing hearts by adenoviral gene transfer: a prototype for gene therapy for disorders of cardiac excitability and contractility. (1996)

Heart failure is a common, often lethal disorder in which conventional pharmacologic strategies have achieved limited success. Failing hearts exhibit a delay of electrical repolarization which predisposes to fatal arrhythmias. To explore the feasibility of gene therapy for this condition, we isolated myocytes from normal and failing dog hearts and quantified electrophysiologic and contractile parameters in primary culture. Action potentials were prolonged in failing cells as a result of diminished potassium currents. Exposure to AdShK, an adenovirus that overexpresses potassium channels, reversed the action potential prolongation of failing cells. The precise phenotype varied as a function of the density of expressed channels; modest increases in potassium current sufficed to mimic the non-diseased state most faithfully, while more robust expression of the transgene excessively abbreviated excitation and contraction. Our results demonstrate that viral gene transfer can modify the electrical properties of adult mammalian heart cells in a manner appropriate to reverse a fundamental disorder of excitability. Realistic application of this form of therapy will need to include a sensitive mechanism for control of the level and distribution of transgene expression.
Bocavirus Infection Induces a DNA Damage Response That Facilitates Viral DNA Replication and Mediates Cell Death (2010)

ABSTRACT Minute virus of canines (MVC) is an autonomous parvovirus that replicates efficiently without helper viruses in Walter Reed/3873D (WRD) canine cells. We previously showed that MVC infection induces mitochondrion-mediated apoptosis and G 2 /M-phase arrest in infected WRD cells. However, the mechanism responsible for these effects has not been established. Here, we report that MVC infection triggers a DNA damage response in infected cells, as evident from phosphorylation of H2AX and RPA32. We discovered that both ATM (ataxia telangiectasia-mutated kinase) and ATR (ATM- and Rad3-related kinase) were phosphorylated in MVC-infected WRD cells and confirmed that ATM activation was responsible for the phosphorylation of H2AX, whereas ATR activation was required for the phosphorylation of RPA32. Both pharmacological inhibition of ATM activation and knockdown of ATM in MVC-infected cells led to a significant reduction in cell death, a moderate correction of cell cycle arrest, and most importantly, a reduction in MVC DNA replication and progeny virus production. Parallel experiments with an ATR-targeted small interfering RNA (siRNA) had no effect. Moreover, we identified that this ATM-mediated cell death is p53 dependent. In addition, we localized the Mre11-Rad50-Nbs1 (MRN) complex, the major mediator as well as a substrate of the ATM-mediated DNA damage response pathway to MVC replication centers during infection, and show that Mre11 knockdown led to a reduction in MVC DNA replication. Our findings are the first to support the notion that an autonomous parvovirus is able to hijack the host DNA damage machinery for its own replication and for the induction of cell death.
Human Stanniocalcin Inhibits Renal Phosphate Excretion in the Rat (1997)

Stanniocalcin (STC) is a glycoprotein hormone first identified in bony fishes where it counteracts hypercalcemia by inhibiting gill calcium uptake and stimulating renal inorganic phosphate (Pi) reabsorption. Human STC (hSTC) has recently been cloned and sequenced and is highly homologous to the fish hormone at the amino acid level. The objective of this study was to examine the possible effects of hSTC on electrolyte homeostasis and renal function in the rat. Recombinant hSTC was expressed in bacteria and purified by metal-ion affinity chromatography and reverse-phase high performance liquid chromatography. Anesthetized animals were given bolus infusions of 1, 5, or 10 nmol hSTC per kilogram of body weight. Control animals received solvent alone. The most effective dosage was 5 nmol/kg, which caused significant reductions in both absolute and fractional phosphate excretion in comparison with control rats. The hSTC had no effect on the renal excretion of other ions, the glomerular filtration rate, renal blood flow, blood pressure, or plasma electrolytes (Na+, K+, Ca2+, Pi, Mg/+). The maximum effect of hSTC on phosphate excretion was observed 60-80 minutes postinjection. Lesser effects were obtained with higher and lower dosages of hormone. When renal cortical brush-border membrane vesicles were isolated from control and hormone-treated animals 80 minutes postinjection, the rate of Na+/Pi cotransport was found to be 40% higher in vesicles from hormone-treated animals (p < 0.01; 5 nmol hSTC/kg). Together, the renal clearance and membrane vesicle data indicate that hSTC participates in the renal regulation of Pi homeostasis in mammals.
Micro total analysis systems 2004 : proceedings of μTAS 2004 8th International Conference on Miniaturized Systems for Chemistry and Life Sciences, Malmö, Sweden, September 26-30, 2004 (2004)

MEMS Technology I Materials Pumping Protein Crystallization Cell Lysis Separation Gene Analysis NMR Applications III MEMS Technology II Detection Techniques Two-Phase Systems Coupling to MS Cell Culture II Analysis Microfluidics, Others On-Chip Monitoring Author Index Key Word Index
Very low pressure chemical vapor deposition process for selective titanium silicide films (1988)

We report for the first time the selective deposition of titanium silicide using a very low pressure chemical vapor deposition technique with silane and titanium tetrachloride as the silicon and titanium sources, respectively. A method is described for the blanket and selective deposition of titanium silicide. A thin polycrystalline silicon (polysilicon) layer is deposited prior to the silicide deposition to promote the nucleation of titanium silicide. It is shown that selective deposition is possible by controlling the polysilicon and the titanium silicide deposition times. The resulting titanium silicide films have resistivities in the range of 15–25 μΩ cm.
Assessment of helical interfaces in protein–protein interactions (2009)

Herein we identify and analyze helical protein interfaces as potential targets for synthetic modulators of protein-protein interactions.
Trans fat feeding results in higher serum alanine aminotransferase and increased insulin resistance compared with a standard murine high-fat diet (2009)

Diets high in trans fats are associated with an increased risk of cardiovascular disease and components of the metabolic syndrome. The influence of these toxic fatty acids on the development of nonalcoholic fatty liver disease has not been significantly examined. Therefore, we sought to compare the effect of a murine diet high in trans fat to a standard high-fat diet that is devoid of trans fats but high in saturated fats. Male AKR/J mice were fed a calorically identical trans fat diet or standard high-fat diet for 10 days, 4 wk, and 8 wk. Serum alanine aminotransferase (ALT), lipid, insulin, and leptin levels were determined and the quantitative insulin-sensitivity check index (QUICKI) was calculated as a measure of insulin resistance. Additionally, hepatic triglyceride content and gene expression of several proinflammatory genes were assessed. By 8 wk, trans fat-fed mice exhibited higher ALT values than standard high-fat-fed mice (126 +/- 16 vs. 71 +/- 7 U/l, P < 0.02) despite similar hepatic triglyceride content at each time point. Trans fat-fed mice also had increased insulin resistance compared with high-fat-fed mice at 4 and 8 wk with significantly higher insulin levels and lower QUICKI values. Additionally, hepatic interleukin-1beta (IL-1beta) gene expression was 3.6-fold higher at 4 wk (P < 0.05) and 5-fold higher at 8 wk (P < 0.05) in trans fat-fed mice compared with standard high-fat-fed mice. Trans fat feeding results in higher ALT values, increased insulin resistance, and elevated IL-1beta levels compared with standard high-fat feeding.
Implications of EMF Exposure Limits on Output Power Levels for 5G Devices Above 6 GHz (2015)

Spectrum is a scarce resource, and the interest for utilizing frequency bands above 6 GHz for future radio communication systems is increasing. The possible use of higher frequency bands implies new challenges in terms of electromagnetic field (EMF) exposure assessments since the fundamental exposure metric (basic restriction) is changing from specific absorption rate (SAR) to power density. In this study, the implication of this change is investigated in terms of the maximum possible radiated power (P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> ) from a device used in close proximity to the human body. The results show that the existing exposure limits will lead to a non-physical discontinuity of several dB in P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> as the transition is made from SAR to power density based basic restrictions. As a consequence, to be compliant with applicable exposure limits at frequencies above 6 GHz, P <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">max</sub> might have to be several dB below the power levels used for current cellular technologies. Since the available power in uplink has a direct impact on the system capacity and coverage, such an inconsistency, if not resolved, might have a large effect on the development of the next generation cellular networks (5G).
CGG repeat in the FMR1 gene: size matters (2011)

The FMR1 gene contains a CGG repeat present in the 5'-untranslated region which can be unstable upon transmission to the next generation. The repeat is up to 55 CGGs long in the normal population. In patients with fragile X syndrome (FXS), a repeat length exceeding 200 CGGs (full mutation: FM) generally leads to methylation of the repeat and the promoter region, which is accompanied by silencing of the FMR1 gene. The absence of FMR1 protein, FMRP, seen in FM is the cause of the mental retardation in patients with FXS. The premutation (PM) is defined as 55-200 CGGs. Female PM carriers are at risk of developing primary ovarian insufficiency. Elderly PM carriers might develop a progressive neurodegenerative disorder called fragile X-associated tremor/ataxia syndrome (FXTAS). Although arising from the mutations in the same gene, distinct mechanisms lead to FXS (absence of FMRP), FXTAS (toxic RNA gain-of-function) and FXPOI. The pathogenic mechanisms thought to underlie these disorders are discussed. This review gives insight on the implications of all possible repeat length categories seen in fragile X families.
Scattering of electrons by the quantised bulk plasma modes in electronically dense materials (1986)

It is shown how explicit field quantisation of bulk plasma modes can be carried out from first principles when the theory is based on the continuum jellium model with spatial dispersion. A canonical transformation, motivated by classical correspondence, is first carried out on the system consisting of the bulk modes in interaction with a charged particle. This transformation effectively incorporates the charge and the bulk field into redefined states of the system in a manner which is analogous to the Power-Zienau transformation of quantum optics. When the transformed theory is applied to the scattering of electrons by the bulk plasmons it more readily enables the screening effects to be taken into account. The shape of the energy-loss-spectrum and its dependence on the momentum transfer are shown to be in satisfactory agreement with available experimental data on metals.
Identification of CD46 Binding Sites within the Adenovirus Serotype 35 Fiber Knob (2007)

ABSTRACT Species B human adenoviruses (Ads) are often associated with fatal illnesses in immunocompromised individuals. Recently, species B Ads, most of which use the ubiquitously expressed complement regulatory protein CD46 as a primary attachment receptor, have gained interest for use as gene therapy vectors. In this study, we focused on species B Ad serotype 35 (Ad35), whose trimeric fiber knob domain binds to three CD46 molecules with a K D (equilibrium dissociation constant) of 15.5 nM. To study the Ad35 knob-CD46 interaction, we generated an expression library of Ad35 knobs with random mutations and screened it for CD46 binding. We identified four critical residues (Phe242, Arg279, Ser282, and Glu302) which, when mutated, ablated Ad35 knob binding to CD46 without affecting knob trimerization. The functional importance of the identified residues was validated in surface plasmon resonance and competition binding studies. To model the Ad35 knob-CD46 interaction, we resolved the Ad35 knob structure at 2-Å resolution by X-ray crystallography and overlaid it onto the existing structure for Ad11-CD46 interaction. According to our model, all identified Ad35 residues are in regions that interact with CD46, whereby one CD46 molecule binds between two knob monomers. This mode of interaction might have potential consequences for CD46 signaling and intracellular trafficking of Ad35. Our findings are also fundamental for better characterization of species B Ads and design of antiviral drugs, as well as for application of species B Ads as in vivo and in vitro gene transfer vectors.
Sigmatropic rearrangements of 2,4-dinitrophenyl oximes (2003)

Reaction of 6-amino-1,3-dimethyluracil (14) with the 2,4-dinitrophenyl oxime (21) of iodoacetone led to initial condensation followed by an unexpected [3,3] sigmatropic rearrangement, followed in turn by ring closure to give 5-(2-hydroxy-3,5-dinitrophenyl)-1,3,6trimethylpyrrolo[2,3-d]pyrimidine-2,4(1H,3H)-dione (22). 6-Methylamino-1,3-dimethyluracil under the same conditions underwent a similar sigmatropic rearrangement, but the product cyclised instead to give 1,3-dimethyl-6-methylamino-5-(2methyl-5,7-dinitro-3-benzo[b]furanyl)pyrimidine-2,4(1H,3H)-dione (32). A third type of product, 4-amino-6-(2-hydroxy-3,5-dinitrophenyl)-5-methyl-2-phenylfuro [2,3-d]pyrimidine (35), was obtained when 6-amino-2-phenyl-4(3H)-pyrimidinone (33) reacted with the 2,4dinitrophenyl oxime (19) of chloroacetone in presence of potassium iodide. Mechanisms are suggested for these unusual reactions.
Improvement of different vaccine delivery systems for cancer therapy (2011)

Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs) have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs) such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP) have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.
Increased synthesis of hyaluronic acid by mouse mammary carcinoma cell variants with high metastatic potential. (1983)

Variant subpopulations of FM3A mouse mammary carcinoma cells that have increased lung-colonizing potential were obtained previously by sequentially harvesting pulmonary metastases, culturing their cells in vitro, and reestablishing the metastases in vivo. In the present study, glycosaminoglycan production by the parental and variant cells was studied after metabolic labeling of cultures by [14C]glucosamine for 24 hr. Analysis of the products indicated that the rate of incorporation of the labeled precursor into hyaluronic acid in the high-metastatic variant cells was 27 to 54 times the rate in the low-metastatic variant cells and that the increase in hyaluronic acid synthesis was not associated with an increase in the rate of synthesis of other glycosaminoglycans. Both the cell layers and media of high-metastatic variants contained a much higher proportion of radioactivity in hyaluronic acid than did the corresponding fractions of low-metastatic cell lines. The results provide a basis for further investigation of the potential role of hyaluronic acid in control of the behavior of epithelial tumor cells during metastasis.