gebhart/patrepeval huggingface dataset:
in vivo quantitative FRET small animal imaging: intensity versus lifetime-based FRET (2023)

Förster Resonance Energy Transfer (FRET) microscopy is used in numerous biophysical and biomedical applications to monitor inter- and intramolecular interactions and conformational changes in the 2-10 nm range. FRET is currently being extended to <i>in vivo</i> optical imaging, its main application being in quantifying drug-target engagement or drug release in animal models of cancer using organic dye or nanoparticle-labeled probes. Herein, we compared FRET quantification using intensity-based FRET (sensitized emission FRET analysis with the 3-cube approach using an IVIS imager) and macroscopic fluorescence lifetime (MFLI) FRET using a custom system using a time-gated ICCD, for small animal optical <i>in vivo</i> imaging. The analytical expressions and experimental protocols required to quantify the product <i>f <sub>D</sub> E</i> of the FRET efficiency <i>E</i> and the fraction of donor molecules involved in FRET, <i>f <sub>D</sub></i> , are described in detail for both methodologies. Dynamic <i>in vivo</i> FRET quantification of transferrin receptor-transferrin binding was acquired in live intact nude mice upon intravenous injection of near infrared-labeled transferrin FRET pair and benchmarked against <i>in vitro</i> FRET using hybridized oligonucleotides. Even though both <i>in vivo</i> imaging techniques provided similar dynamic trends for receptor-ligand engagement, we demonstrate that MFLI FRET has significant advantages. Whereas the sensitized emission FRET approach using the IVIS imager required 9 measurements (6 of which are used for calibration) acquired from three mice, MFLI FRET needed only one measurement collected from a single mouse, although a control mouse might be needed in a more general situation. Based on our study, MFLI therefore represents the method of choice for longitudinal preclinical FRET studies such as that of targeted drug delivery in intact, live mice.
A theoretical characterization of nonlinear distortion effects in OFDM systems (2000)

This paper presents a theoretical characterization of nonlinear distortion effects in orthogonal frequency division multiplexing (OFDM) transmission systems. In the theoretical framework developed, it is shown that the effects on the decision variables of the in-band distortion introduced by a bandpass memoryless nonlinearity can be described by means of a complex gain and an additive Gaussian term with zero mean and suitable variance; analytical expressions for gain and variance are given. The conditions which allow this description are emphasized and discussed. As a consequence, a completely analytical procedure to evaluate error probability is also obtained and illustrated using OFDM/discrete multitone modulation (DMT) systems with rectangular pulse shaping; for the soft-envelope limiter nonlinearity, a closed form is derived. A comparison with simulation results is carried out to verify the accuracy of this method.
Increased AT1receptor expression and mRNA in kidney glomeruli of AT2receptor gene-disrupted mice (2001)

The proposed feedback between angiotensin II AT(2) and AT(1) receptors prompted us to study AT(1) receptor expression in kidneys of male AT(2) receptor-gene disrupted mice (agtr2 -/y). In wild-type (agtr2 +/y) mice, AT(1) receptor binding and mRNA is abundant in glomeruli, and AT(1) receptor binding is also high in the inner stripe of the outer medulla. AT(2) receptors are scarce, primarily associated to cortical vascular structures. In agtr2 -/y mice, AT(1) receptor binding and mRNA were increased in the kidney glomeruli, and AT(1) receptor binding was higher in the rest of the cortex and outer stripe of the outer medulla, but not in its inner stripe, indicating different cellular regulation. Although AT(2) receptor expression is very low in male agtr 2 +/y mice, their gene disruption alters AT(1) receptor expression. AT(1) upregulation alone may explain the AT(2) gene-disrupted mice phenotype such as increased blood pressure, higher sensitivity to angiotensin II, and altered renal function. The indirect AT(1)/AT(2) receptor feedback could have clinical significance because AT(1) antagonists are widely used in medical practice.
Determination of the glass transition temperature of photorefractive polymer composites from photoconductivity measurements (2008)

A method to determine the glass transition temperature (Tg) of photorefractive (PR) polymer composites, based on photoconductivity measurements, is proposed. The composite Tg is identified as the temperature at which a clear change in slope in the Arrhenius plot representation of the photoconductivity is obtained. We demonstrate that for PR polymers, this method is more appropriate than the one generally used, based on differential scanning calorimetry (DSC). For PR composites based on the hole transporting polymer poly(N-vinylcarbazole), the Tg value determined from photoconductivity data is around 30°C higher than that obtained by DSC.
Insulin-Like Growth Factor Binding Proteins-3 and -5: Central Mediators of Fibrosis and Promising New Therapeutic Targets (2012)

Fibrosis involves an orchestrated cascade of events including activation of fibroblasts, increased production and deposition of extracellular matrix components, and differentiation of fibroblasts into myofibroblasts. Epithelial-mesenchymal cross-talk plays an important role in this process, and current hypotheses of organ fibrosis liken it to an aberrant wound healing response in which epithelial-mesenchymal transition (EMT) and cellular senescence may also contribute to disease pathogenesis. The fibrotic response is associated with altered expression of growth factors and cytokines, including increased levels of transforming growth factor-β1 (TGF-β1) and the more recent observation that increased levels of several insulin-like growth factor binding proteins (IGFBPs) are associated with a number of fibrotic conditions. IGFBPs have been implicated in virtually every cell type and process associated with the fibrotic response, making the IGFBPs attractive targets for the development of novel anti-fibrotic therapies. In this review, the current state of knowledge regarding the classical IGFBP family in organ fibrosis will be summarized and the clinical implications considered.
Human platelet-derived growth factor: structure and function. (1983)

Human platelet-derived growth factor (PDGF) is a heat-stable, cationic polypeptide transported in blood in the alpha granules of platelets. It is released from platelets during blood clotting. PDGF has been resolved into at least two closely related active polypeptides, PDGF-I and PDGF-II, each consisting of two inactive chains linked together by disulfide bonds. PDGF stimulates the growth of normal cells in culture, including fibroblasts, arterial smooth muscle cells, and glial cells. In addition, PDGF has been shown to stimulate cell migration and many diverse metabolic functions such as amino acid transport, protein synthesis, cholesterol ester synthesis, phospholipid turnover, and prostacyclin synthesis. It modulates receptor binding of other active components such as epidermal growth factor, luteinizing hormone, low-density lipoprotein, and somatomedin C. Specific cell membrane receptors for PDGF have been demonstrated in arterial smooth muscle cells and fibroblasts.
Vitamin K epoxide reductase and its paralogous enzyme have different structures and functions (2020)

Vitamin K epoxide reductase (VKOR) is an essential enzyme for vitamin K-dependent carboxylation, while the physiological function of its paralogous enzyme VKOR-like (VKORL) is yet unknown. Although these two enzymes share approximately 50% protein sequence homology, the membrane topology of VKOR is still in debate. Here, we explored the differences in the membrane topology and disulfide-linked oligomerization of these two enzymes. Results from mutating the critical amino acid residues in the disputed transmembrane (TM) regions revealed that the second TM domain in the proposed 4-TM model of VKOR does not function as an authentic TM helix; supporting VKOR is a 3-TM protein, which is different from VKORL. Additionally, altering the loop sequence between the two conserved cysteine residues of VKORL affects its activity, supporting the notion that the conserved loop cysteines of VKORL are involved in its active site regeneration. However, a similar mutation in VKOR does not affect its enzymatic activity. Finally, our results show that although both VKOR and VKORL form disulfide-linked oligomers, the cysteine residues involved in the oligomerization appear to be different. Overall, the structural and functional differences between VKOR and VKORL shown here indicate that VKORL might have a different physiological function other than recycling vitamin K.
Three‐Dimensional Structure and Properties of Wild‐Type and Mutant H‐ ras ‐Encoded p21 (2007)

Ras (or p21) is the product of the ras proto-oncogene and is believed to be involved in growth-promoting signal transduction. The structure of the guanine nucleotide-binding domain of H-Ras (or p21H-ras) in the triphosphate conformation was determined at very high resolution (1.4 A). All the binding interactions between protein and Gpp[NH]p and Mg2+ can be resolved in great detail. The region around amino acids 61-65 is flexible and exists in two conformations, one of which seems to be important for catalysis. The properties and structures of several oncogenic and non-oncogenic mutant forms of Ras have also been determined. Since the structure of the GDP-bound form is also known, the nature of the conformational change from the GTP-bound to the GDP-bound form can be inferred from the 3-D structure. A mechanism for the intrinsic GTP hydrolysis has been proposed. Its implications for the GAP-stimulated GTPase reaction is discussed in the light of recent kinetic and mutational experiments.
Influence of Iron Substitutions on the Transport Properties of FeTe_{0.65}Se_{0.35} Single Crystals (2014)

We study the ab-plane resistivity and Hall eect in the single crystals of , where M = Co or Ni (0 y 0.21). In case of each dopant two types of crystals, with dierent crystalline quality, are prepared by Bridgman's method using dierent cooling rates, fast or slow. The impurities suppress the superconducting transition temperature, Tc, with dierent rates. Tc reaches zero at markedly dierent impurity content: only 3 at.% of Ni, and about 14 at.% of Co. In addition, the suppression is somewhat dependent on the crystal cooling rate. The resistivity at the onset of superconductivity rises only weakly with the Co doping, while it increases 10 times faster for Ni. The Hall coecient RH is positive for Co doping indicating that hole carriers dominate the transport. For Ni RH changes sign into negative at low temperatures for crystals with the Ni content exceeding 6 at.%. The implications of these results are discussed.
An Oxygen‐Tolerant PET‐RAFT Polymerization for Screening Structure–Activity Relationships (2018)

The complexity of polymer-protein interactions makes rational design of the best polymer architecture for any given biointerface extremely challenging, and the high throughput synthesis and screening of polymers has emerged as an attractive alternative. A porphyrin-catalysed photoinduced electron/energy transfer-reversible addition-fragmentation chain-transfer (PET-RAFT) polymerisation was adapted to enable high throughput synthesis of complex polymer architectures in dimethyl sulfoxide (DMSO) on low-volume well plates in the presence of air. The polymerisation system shows remarkable oxygen tolerance, and excellent control of functional 3- and 4-arm star polymers. We then apply this method to investigate the effect of polymer structure on protein binding, in this case to the lectin concanavalin A (ConA). Such an approach could be applied to screen the structure-activity relationships for any number of polymer-protein interactions.
Toward scalable simulations of lattice gauge theories on quantum computers (2020)

The simulation of real-time dynamics in lattice gauge theories is particularly hard for classical computing due to the exponential scaling of the required resources. On the other hand, quantum algorithms can potentially perform the same calculation with a polynomial dependence on the number of degrees of freedom. A precise estimation is however particularly challenging for the simulation of lattice gauge theories in arbitrary dimensions, where gauge fields are dynamical variables, in addition to the particle fields. Moreover, there exist several choices for discretizing particles and gauge fields on a lattice, each of them coming at different prices in terms of qubit register size and circuit depth. Here we provide a resource counting for real-time evolution of $U(1)$ gauge theories, such as quantum electrodynamics, on arbitrary dimension using the Wilson fermion representation for the particles, and the quantum link model approach for the gauge fields. We study the phenomena of flux-string breaking up to a genuine bidimensional model using classical simulations of the quantum circuits and discuss the advantages of our discretization choice in simulation of more challenging $SU(N)$ gauge theories such as quantum chromodynamics.
IP Protection and Supply Chain Security through Logic Obfuscation (2019)

The globalization of the semiconductor supply chain introduces ever-increasing security and privacy risks. Two major concerns are IP theft through reverse engineering and malicious modification of the design. The latter concern in part relies on successful reverse engineering of the design as well. IC camouflaging and logic locking are two of the techniques under research that can thwart reverse engineering by end-users or foundries. However, developing low overhead locking/camouflaging schemes that can resist the ever-evolving state-of-the-art attacks has been a challenge for several years. This article provides a comprehensive review of the state of the art with respect to locking/camouflaging techniques. We start by defining a systematic threat model for these techniques and discuss how various real-world scenarios relate to each threat model. We then discuss the evolution of generic algorithmic attacks under each threat model eventually leading to the strongest existing attacks. The article then systematizes defences and along the way discusses attacks that are more specific to certain kinds of locking/camouflaging. The article then concludes by discussing open problems and future directions.
Global Suppression of the Host Antiviral Response by Ebola- and Marburgviruses: Increased Antagonism of the Type I Interferon Response Is Associated with Enhanced Virulence (2006)

We studied the effect of filovirus infection on host cell gene expression by characterizing the regulation of gene expression responses in human liver cells infected with Zaire Ebolavirus (ZEBOV), Reston Ebolavirus (REBOV), and Marburgvirus (MARV), using transcriptional profiling and bioinformatics. Expression microarray analysis demonstrated that filovirus infection resulted in the up-regulation of immune-related genes and the down-regulation of many coagulation and acute-phase proteins. These studies further revealed that a common feature of filovirus virulence is suppression of key cellular antiviral responses, including TLR-, interferon (IFN) regulatory factor 3-, and PKR-related pathways. We further showed that ZEBOV and MARV were more potent antagonists of the IFN response and inhibited the expression of most of the IFN-stimulated genes (ISGs) observed in mock-infected IFN-alpha-2b treated cells, compared to REBOV infection, which activated more than 20% of these ISGs. Finally, we examined IFN-related gene expression in filovirus-infected cells treated with IFN-alpha-2b. These experiments revealed that a majority of genes induced in mock-infected cells treated with type I IFN were antagonized in treated ZEBOV- and MARV-infected cells, while in contrast, REBOV infection resulted in a significant increase in ISG expression. Analysis of STAT1 and -2 phosphorylation following IFN treatment showed a significant reduction of STAT phosphorylation for MARV but not for ZEBOV and REBOV, indicating that different mechanisms might be involved in antagonizing IFN signaling pathways by the different filovirus species. Taken together, these studies showed a correlation between antagonism of type I IFN responses and filovirus virulence.
Improvement of hyperadrenergic postural orthostatic tachycardia syndrome (POTS) with methylated B vitamins in the setting of a heterozygous COMT Val158Met polymorphism (2021)

A middle-aged woman was diagnosed with postural orthostatic tachycardia syndrome based on her clinical symptoms, elevated norepinephrine levels and positive tilt-table test. The patient was refractory to conventional treatment and improved only after she was treated with methylated B vitamins for her heterozygous catechol-O-methyltransferase Val158Met polymorphism.
Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro (2020)

In December 2019, a novel pneumonia caused by a previously&#13;\nunknown pathogen emerged in Wuhan, a city of 11 million&#13;\npeople in central China. The initial cases were linked to&#13;\nexposures in a seafood market in Wuhan.1 As of January 27,&#13;\n2020, the Chinese authorities reported 2835 confirmed cases in&#13;\nmainland China, including 81 deaths. Additionally, 19 confirmed&#13;\ncases were identified in Hong Kong, Macao and Taiwan, and 39&#13;\nimported cases were identified in Thailand, Japan, South Korea,&#13;\nUnited States, Vietnam, Singapore, Nepal, France, Australia&#13;\nand Canada. The pathogen was soon identified as a novel&#13;\ncoronavirus (2019-nCoV), which is closely related to sever acute&#13;\nrespiratory syndrome CoV (SARS-CoV).2 Currently, there is no&#13;\nspecific treatment against the new virus. Therefore, identifying&#13;\neffective antiviral agents to combat the disease is urgently&#13;\nneeded.
Polymerization of Lipid Bilayer Initiated by a Redox Initiator: Effect of Polymerization on Dyes in the Inner Water Phase (1990)

Abstract The polymerization of the liposomal lipid bilayers of phoshpolipids having one or two diene groups was studied by the use of a redox initiator (NaHSO3/K2S2O8) at low temperature (8 °C). The soluble and insoluble polymers were obtained, respectively. The membrane polymerization itself had small effect on the dye in the inner water phase.
Beneficial effects of fingolimod in MS patients with high serum Sema4A levels (2018)

We previously demonstrated that patients with multiple sclerosis (MS) of high serum Sema4A levels are resistant to IFN-β therapy. To further elucidate the role of serum Sema4A as a biomarker for therapeutic stratification in MS patients, it is important to clarify the efficacy of other disease-modifying drugs (DMD) in those with high serum Sema4A levels. Thus, in this study we investigated whether fingolimod has beneficial effects on MS patients with high Sema4A levels. We retrospectively analyzed annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) change in 56 relapsing-remitting multiple sclerosis (RRMS) patients who had been treated with fingolimod, including those who switched from IFN-β therapy. The levels of Sema4A in the sera were measured by sandwich ELISA. The implications of Sema4A on the efficacy of fingolimod were investigated by administering recombinant Sema4A-Fc and fingolimod to mice with experimental autoimmune encephalomyelitis (EAE). Retrospective analysis of MS cohort (17 high Sema4A and 39 low Sema4A) demonstrated the effectiveness of fingolimod in those with high serum Sema4A levels, showing reduction of ARR (from 1.21 to 0.12) and EDSS progression (from 0.50 to 0.04). Consistent with this observation, improvement in the disease severity of EAE mice receiving recombinant Sema4A-Fc was also observed after fingolimod treatment. These data suggest that fingolimod could serve as a candidate DMD for managing the disease activity of MS patients with high Sema4A levels.
Chemical constituents from Zanthoxylum setulosum (Rutaceae) (2011)

"Following our phytochemical studies of Costa Rican plants, in this work we report the isolation and identification of eight compounds from aerial parts of Zanthoxylum setulosum (Rutaceae). They were identified as the alkaloid skimmianine, the lignans savinin, kusunokinin, sesamin, syringaresinol and the isopentenyl ether of pluviatol, the amide aurantiamide acetate, and the triterpen lupeol. This is the first report of isolation of skimmianine from the leaves of Z. setulosum and its presence confirm that quinoline and benzophenanthridine alkaloids, can be considered as chemotaxonomic markers of this genus. All the isolated compounds were characterized by spectroscopic methods (including 1H-NMR, 13C-NMR, , HMQC, HMBC and NOESY) and comparison with the literature data."
Peripheral Vascular Occlusions Leading to Gangrene and Amputations in Antiphospholipid Antibody Positive Patients (2007)

Twenty-one cases from several medical centers (Brazil, Italy, Serbia, South Africa, Israel, and the United Kingdom) with severe peripheral vascular disease progressing to amputations of limbs/digits, all of whom tested positive for antiphospholipid antibodies, are documented. The patients were suffering from either systemic lupus erythematosus, discoid LE, "primary" antiphospholipid syndrome (PAPS), "lupus-like" disease, undifferentiated connective tissue disease. A high frequency of livedo reticularis preceding the arterial occlusions in our series of patients who subsequently progressed to ischemic necrosis and amputation of limbs/digits was noted. Five of the 10 patients, in whom histopathological studies had been performed, demonstrated the typical vasculopathy seen with the antiphospholipid syndrome ("APS vasculopathy"). Complicating vasculitis was present in seven of the patients. Five of the patients developed severe peripheral vascular disease during the course of the catastrophic antiphospholipid (Asherson's) syndrome.
Prelimary Data for Suppression of Secondary Electron yield (2018)

The multipactor effect is a discharge phenomenon which may occur when secondary electron emission (SEE) is in resonance with an electric field under certain vacuum conditions [1]. Liberated electrons will oscillate between two surfaces driven by a radio frequency (RF) field; this discharge cultivates and sustains itself by SEE through reoccurring impacts with the surface. This can lead to deterioration of vacuum RF electronics' performance [2]. To suppress the multipactor effect, the secondary electron yield (SEY) must be reduced.
Stretchable strain sensor based on metal nanoparticle thin film for human motion detection &amp; flexible pressure sensing devices (2013)

Stretchable strain sensor can be used as wearable motion detection device and the sensing element of flexible pressure sensor. We made the stretchable strain sensor by single-step direct transfer/patterning process which is simple and low-cost fabrication method. Metal nanoparticle ink as sensing material was transferred onto polydimethylsiloxane (PDMS) and the opening/closure of its micro-cracks is believed to be the mechanism of our stretchable strain sensor. Also, we demonstrated the potential of stretchable strain sensor as human motion detector and flexible pressure sensor.