gebhart/patrepeval huggingface dataset:
Secondary metabolite from <i><scp>N</scp>ostoc</i> <scp>XPORK14A</scp> inhibits photosynthesis and growth of <i><scp>S</scp>ynechocystis</i> <scp>PCC</scp> 6803 (2013)

Screening of 55 different cyanobacterial strains revealed that an extract from Nostoc XPORK14A drastically modifies the amplitude and kinetics of chlorophyll a fluorescence induction of Synechocystis PCC6803 cells.After 2 d exposure to the Nostoc XPORK14A extract, Synechocystis PCC 6803 cells displayed reduced net photosynthetic activity and significantly modified electron transport properties of photosystem II under both light and dark conditions. However, the maximum oxidizable amount of P700 was not strongly affected. The extract also induced strong oxidative stress in Synechocystis PCC 6803 cells in both light and darkness. We identified the secondary metabolite of Nostoc XPORK14A causing these pronounced effects on Synechocystis cells. Mass spectrometry and nuclear magnetic resonance analyses revealed that this compound, designated as M22, has a non-peptide structure. We propose that M22 possesses a dualaction mechanism: firstly, by photogeneration of reactive oxygen species in the presence of light, which in turn affects the photosynthetic machinery of Synechocystis PCC 6803; and secondly, by altering the in vivo redox status of cells, possibly through inhibition of protein kinases.
Switchable Plasmonic–Dielectric Resonators with Metal–Insulator Transitions (2017)

Nanophotonic resonators offer the ability to design nanoscale optical elements and engineered materials with unconventional properties. Dielectric-based resonators intrinsically support a complete multipolar resonant response with low absorption, while metallic resonators provide extreme light confinement and enhanced photon–electron interactions. Here, we construct resonators out of a prototypical metal–insulator transition material, vanadium dioxide (VO2), and demonstrate switching between dielectric and plasmonic resonances. We first characterize the temperature-dependent infrared optical constants of VO2 single crystals and thin-films. We then fabricate VO2 wire arrays and disk arrays. We show that wire resonators support dielectric resonances at low temperatures, a damped scattering response at intermediate temperatures, and plasmonic resonances at high temperatures. In disk resonators, however, upon heating, there is a pronounced enhancement of scattering at intermediate temperatures and a substantial narrowing of the phase transition. These findings may lead to the design of novel nanophotonic devices that incorporate thermally switchable plasmonic–dielectric behavior.
Performance of a Coaxial Swirl Injector with Flow Path Reversal (2005)

Liquid Propulsion Systems Centre has developed 22N and 10N bi-propellant thrusters employing hypergolic propellant combination of NTO as oxidizer and MMH as fuel. Coaxial swirl injector is used in these thrusters with oxidizer flowing through the inner swirl passage and fuel through the outer swirl passage. In order to enhance the thruster performance and to make it less sensitive to fabrication deviations, different configurations of injector were studied. In the first phase of investigation , fuel was allowed to flow through the outer swirl passage and oxidizer through the inner swirl passage. The difference between the inner and outer flow cone angles was varied by altering the surface finish of critical inner flow passage only. The performance was compiled by conducting cold flow studies and hot firing tests. In the second phase, injector dimensions were modified for flow path reversal to allow oxidizer flow through the outer passage and fuel flow through the inner passage. In this case also a similar experiments were carried out. Deposition of carbonaceous particles which was observed on the injector face while oxidizer flowed through the inner swirl passage disappeared when oxidizer was admitted through the outer passage.The specific impulse also improved by as much as 10secs and was found to be insensitive to minor variations in the inner flow cone angles. The results are discussed in this report.
The Combination of a Novel GLUT1 Inhibitor and Cisplatin Synergistically Inhibits Breast Cancer Cell Growth By Enhancing the DNA Damaging Effect and Modulating the Akt/mTOR and MAPK Signaling Pathways (2022)

Breast cancer is the most prevalent cancer and the second leading cause of cancer death in women. Cisplatin is a commonly used chemotherapeutic drug for breast cancer treatment. Owing to serious side effects, the combination of cisplatin with other drugs is an effective strategy to simultaneously reduce side effects and increase the anticancer efficacy. GLUT1 is an emerging target for cancer treatment since cancer cells usually consume more glucose, a phenomenon called the Warburg effect. In this study, we found that the combination of cisplatin and a novel GLUT1 inhibitor #43 identified from our previous high-throughput screening exerted a synergistic anticancer effect in MCF-7 and MDA-MB-231 breast cancer cells. Mechanism studies in MCF-7 cells revealed that combination of cisplatin and #43 significantly induced apoptosis, intracellular reactive oxygen species, and loss of mitochondrial membrane potential. Furthermore, #43 enhanced the DNA damaging effect of cisplatin. Akt/mTOR downstream signaling and the ERK signaling pathway usually involved in cell growth and survival were inhibited by the combination treatment. On the other hand, phosphorylation of p38 and JNK, which may be associated with apoptosis, was induced by the combination treatment. Altogether, our data indicate that oxidative stress, DNA damage, the Akt/mTOR and MAPK signaling pathways, and apoptosis may be involved in the synergism of cisplatin and #43 in breast cancer cells.
Similarities and Contrasts in Ryanodine Receptor Localization and Function in Osteoclasts and Striated Muscle Cells (2007)

This review compares ryanodine receptor (RyR)-mediated Ca(2+) signaling processes in muscle and osteoclast cells. In muscle, RyR-mediated release of an intracellularly stored, sarcoplasmic reticular (SR), Ca(2+) is triggered by voltage-sensitive dihydropyridine receptor (DHPR)-L-type Ca(2+) channels either through an allosteric coupling with the RyR in skeletal muscle or a Ca(2+)-induced Ca(2+) release initiated by extracellular Ca(2+) entry in cardiac muscle. Both cell subtypes are nevertheless capable of Ca(2+)-induced SR Ca(2+) release with cardiac muscle additionally showing a store overload-induced Ca(2+) release (SOICR) driven by SR luminal Ca(2+) under some pathological conditions. Osteoclasts similarly show cytosolic Ca(2+) elevations driven by release of intracellular Ca(2+) stores that culminate in motile activity in turn modifying bone resorptive activity. However, such triggering is controlled by ambient Ca(2+) rather than membrane potential with features strongly suggestive of control by a surface membrane Ca(2+) receptor. Yet common actions of the RyR-specific agents perchlorate, dantrolene Na, ryanodine, caffeine, adenosine 3',5'-cyclic diphosphate ribose (cADPr) and ruthenium red implicate RyR in signaling in all these cell types. These findings were reconciled by reports confirming and uniquely localizing a cell surface rather than microsomal osteoclastic RyR that might itself detect ambient Ca(2+) possibly through its otherwise intraluminal positioned low-affinity Ca(2+)-binding site in parallel with the SOICR mechanism in cardiac muscle. Such a mechanism could interact with other osteoclast processes transferring Ca(2+) between cytosol, intracellular stores and extracellular space and be integrated with systemic processes regulating Ca(2+) homeostasis.
Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals (2022)

ABSTRACT Genome-wide association studies (GWAS) of serum metabolites have the potential to uncover genes that influence human metabolism. Here, we combined an integrative genetic analysis associating serum metabolites to membrane transporters with a coessentiality map of metabolic genes. This analysis revealed a connection between feline leukemia virus subgroup C cellular receptor 1 (FLVCR1) - a plasma membrane protein - and phosphocholine, a downstream metabolite of choline metabolism. Loss of FLVCR1 in human cells and in mice strongly impairs choline metabolism due to a block in choline import. Consistently, CRISPR-based genetic screens identified several components of the membrane phospholipid machinery as synthetic lethal with FLVCR1 loss. Finally, cells lacking FLVCR1 exhibit mitochondrial defects and upregulate the integrated stress response (ISR) through heme regulated inhibitors kinase (HRI). Altogether, these findings identify FLVCR1 as a universal mediator of choline transport in mammals and provide a platform to discover substrates for unknown metabolite transporters.
Muscle forces analysis in the shoulder mechanism during wheelchair propulsion (2004)

This study combines an ergometric wheelchair, a six-camera video motion capture system and a prototype computer graphics based musculoskeletal model (CGMM) to predict shoulder joint loading, muscle contraction force per muscle and the sequence of muscular actions during wheelchair propulsion, and also to provide an animated computer graphics model of the relative interactions. Five healthy male subjects with no history of upper extremity injury participated. A conventional manual wheelchair was equipped with a six-component load cell to collect three-dimensional forces and moments experienced by the wheel, allowing real-time measurement of hand/rim force applied by subjects during normal wheelchair operation. An ExpertVision six-camera video motion capture system collected trajectory data of markers attached on anatomical positions. The CGMM was used to simulate and animate muscle action by using an optimization technique combining observed muscular motions with physiological constraints to estimate muscle contraction forces during wheelchair propulsion. The CGMM provides results that satisfactorily match the predictions of previous work, disregarding minor differences which presumably result from differing experimental conditions, measurement technologies and subjects. Specifically, the CGMM shows that the supraspinatus, infraspinatus, anterior deltoid, pectoralis major and biceps long head are the prime movers during the propulsion phase. The middle and posterior deltoid and supraspinatus muscles are responsible for arm return during the recovery phase. CGMM modelling shows that the rotator cuff and pectoralis major play an important role during wheelchair propulsion, confirming the known risk of injury for these muscles during wheelchair propulsion. The CGMM successfully transforms six-camera video motion capture data into a technically useful and visually interesting animated video model of the shoulder musculoskeletal system. The CGMM further yields accurate estimates of muscular forces during motion, indicating that this prototype modelling and analysis technique will aid in study, analysis and therapy of the mechanics and underlying pathomechanics involved in various musculoskeletal overuse syndromes.
Brandt's GLR method &amp; refined HMM segmentation for TTS synthesis application (2005)

In comparison with standard HMM (Hidden Markov Model) with forced alignment, this paper discusses two automatic segmentation algorithms from different points of view: the probabilities of insertion and omission, and the accuracy. The first algorithm, hereafter named the refined HMM algorithm, aims at refining the segmentation performed by standard HMM via a GMM (Gaussian Mixture Model) of each boundary. The second is the Brandt's GLR (Generalized Likelihood Ratio) method. Its goal is to detect signal discontinuities. Provided that the sequence of speech units is known, the experimental results presented in this paper suggest in combining the refined HMM algorithm with Brandt's GLR method and other algorithms adapted to the detection of boundaries between known acoustic classes.
TBIO-19. INTEGRATED GENOMIC, PROTEOMIC AND PHOSPHOPROTEOMIC ANALYSIS OF SEVEN TYPES OF PEDIATRIC BRAIN CANCER (2020)

Abstract We performed a comprehensive proteogenomic analysis across seven childhood brain tumors for a deeper understanding of their functional biology. Whole genome sequencing, RNAseq, quantitative proteomic profiling and phosphoproteomics were performed on 219 fresh frozen tumor samples representing the histologic diagnoses of: low grade astrocytoma (93), ependymoma (32), high grade astrocytoma (26), medulloblastoma (22), ganglioglioma (18), craniopharyngioma (16) and atypical teratoid rhabdoid tumor (12). Unsupervised clustering analysis based on proteomics data reveals eight clusters with distinct protein profiles and pathway activities. While some clusters coincide with histologic diagnoses, a couple of clusters appear to be a mixture of different diagnoses, including one cluster consisting of “aggressive” tumors characterized by poor survival and high stemness scores. By integrating proteomic data with RNAseq and WGS data, we characterize the impact of mutations (H3K27M, BRAFV600E, BRAF fusion) and CNVs upon the proteome across various diagnoses. Multiomics based kinase-substrate association analysis and co-expression network analysis reveal targetable active kinase networks within these tumors. Proteomic data reveals unique biology associated with H3K27M mutation status in HGG and BRAF aberrations in LGG. Characterization of the tumor microenvironment through deconvolution analyses based on multi-omics data reveals 5 distinct tumor clusters associated with different populations of infiltrating immune cells and the relative activity of the immune system based upon the expression of pro-inflammation or immunosuppressive markers. This study reports the first large-scale deep comprehensive proteogenomic analysis crossing traditional histologic boundaries to uncover foundational pediatric brain tumor biology including functional insight that helps drive translational efforts.
P4‐041: Restricted V‐genes Usage of Mouse Humoral Response Against the Efrh Immunodominant Epitope of aβ (2010)

Over the last decade, success in experimental and clinical trials using transgenic mice have provided great hope for antibodies as therapeutic strategies to treat Alzheimer's Disease. Although, these approaches have thus far produced undesirable side effects in humans, antibody therapies remain one of the most promising treatments attracting considerable investment from both academics and pharmaceutical companies. In this study, we analyzed the V-genes of eleven independently isolated monoclonal antibodies raised against the 3EFRH6 sequence, located at the N-terminal region of the amyloid-β-peptide (Aβ). Surprisingly, we found a high and unusual level of restriction in the VH/VL pairing of these antibodies. We designed and produced a range of recombinant Fab constructs by variable domain exchange, HCDR3 loop replacement, germline segment insertion and point mutations. All the Fab fragments were tested and compared by surface plasmon resonance on Aβ1-16 and high molecular weight oligomers. The results emphasize the importance of germline encoded residues and provide insight into how to elicit a humoral immune response in order to generate conformational mouse monoclonal antibodies.
Correlating electronic properties with M-site composition in solid solution Ti<i> <sub>y</sub> </i>Nb<sub>2-</sub> <i> <sub>y</sub> </i>CT<i> <sub>x</sub> </i> MXenes (2022)

Abstract High electrical conductivity is desired in MXene films for applications such as electromagnetic interference shielding, antennas, and electrodes for electrochemical energy storage and conversion applications. Due to the acid etching-based synthesis method, it is challenging to deconvolute the relative importance that factors such as chemical composition and flake size contribute to resistivity. To understand the intrinsic and extrinsic contributions to the macroscopic electronic transport properties, a systematic study controlling compositional and structural parameters was conducted with eight solid solutions in the Ti y Nb 2− y CT x system. In particular, we investigated the different roles played by metal (M)-site composition, flake size, and d -spacing on macroscopic transport. Hard x-ray photoemission spectroscopy and spectroscopic ellipsometry revealed changes to electronic structure induced by the M-site alloying. Consistent with the spectroscopic results, the low- and room-temperature conductivities and effective carrier mobility are correlated with the Ti content, while the impact of flake size and d -spacing is most prominent in low-temperature transport. The results provide guidance for designing and engineering MXenes with a wide range of conductivities.
N-cadherin upregulation mediates adaptive radioresistance in glioblastoma (2021)

Glioblastoma (GBM) is composed of heterogeneous tumor cell populations, including those with stem cell properties, termed glioma stem cells (GSCs). GSCs are innately less radiation sensitive than the tumor bulk and are believed to drive GBM formation and recurrence after repeated irradiation. However, it is unclear how GSCs adapt to escape the toxicity of repeated irradiation used in clinical practice. To identify important mediators of adaptive radioresistance in GBM, we generated radioresistant human and mouse GSCs by exposing them to repeat cycles of irradiation. Surviving subpopulations acquired strong radioresistance in vivo, which was accompanied by a reduction in cell proliferation and an increase in cell-cell adhesion and N-cadherin expression. Increasing N-cadherin expression rendered parental GSCs radioresistant, reduced their proliferation, and increased their stemness and intercellular adhesive properties. Conversely, radioresistant GSCs lost their acquired phenotypes upon CRISPR/Cas9-mediated knockout of N-cadherin. Mechanistically, elevated N-cadherin expression resulted in the accumulation of β-catenin at the cell surface, which suppressed Wnt/β-catenin proliferative signaling, reduced neural differentiation, and protected against apoptosis through Clusterin secretion. N-cadherin upregulation was induced by radiation-induced IGF1 secretion, and the radiation resistance phenotype could be reverted with picropodophyllin, a clinically applicable blood-brain-barrier permeable IGF1 receptor inhibitor, supporting clinical translation.
Theoretical Study on Acylacetanilide Azomethine Dyes: A Relationship between Electronic Absorption Properties and Molecular Structures (2005)

Abstract The relationship between visual absorption properties and molecular structures was investigated for a series of yellow azomethine dyes derived from 4-diethylamino-2-methylaniline and 2-acyl-2′-chloroacetanilides, in which the acyl groups are 1-indolinylcarbonyl (IA), 1-methylcyclopropylcarbonyl (CA), acetyl, benzoyl, and pivaloyl (PA). DFT calculations predicted major conformational isomers attributed to deviations from the planarity of the p-aminophenyl–azomethine fragment. Observed wavelengths were well reproduced by TD-DFT calculations at global minimum geometries, whereas the intensities correlate with the Boltzmann-weighted oscillator strengths. The observed intensities varied by 1.5 times from minimum to maximum without significant shifts in the peak wavelengths, demonstrating the largest absorption of IA and the distinct increase of absorption by changing the acyl group from open- (PA) to closed-ring (CA). The different acyl groups nearly perpendicular to the azomethine fragment in global minima alter frontier orbital energies, while leaving HOMO–LUMO energy gaps almost unchanged. The acyl groups, which are twisted largely in local minima, exert mesomeric effects to lower the LUMO energies. The planarity of the p-aminophenyl–azomethine fragment affects HOMO–LUMO overlapping, but hardly changes HOMO and LUMO energies. These electronic and steric effects rationalize the absorption intensities and peak wavelengths observed for the dyes and also the sharp-cut curves of spectra in the long-wavelength sides for IA and CA.
Time-Skew Hebb Rule in a Nonisopotential Neuron (1995)

In an isopotential neuron with rapid response, it has been shown that the receptive fields formed by Hebbian synaptic modulation depend on the principal eigenspace of Q(0), the input autocorrelation matrix, where Q ij (τ) = 〈ξ i (τ) ξ j (t − T)〉 and ξ i (t) is the input to synapse i at time t (Oja 1982). We relax the assumption of isopotentiality, introduce a time-skewed Hebb rule, and find that the dynamics of synaptic evolution are determined by the principal eigenspace of [Formula: see text]. This matrix is defined by [Formula: see text], where K ij (τ) is the neuron's voltage response to a unit current injection at synapse j as measured τ seconds later at synapse i, and ψ i (τ) is the time course of the opportunity for modulation of synapse i following the arrival of a presynaptic action potential.
Multifunctional Porous Microspheres Based on Peptide–Porphyrin Hierarchical Co‐Assembly (2014)

Photocatalytically active, multi-chambered, biomolecule-based microspheres were prepared by hierarchical co-assembly of simple dipeptides and porphyrins. The colloidal microspheres are highly hydrated and consist of a network of J-aggregate nanoscale substructures that serve as light-harvesting antennae with a relatively broad spectral cross-section and considerable photostability. These optical properties can be exploited in photocatalytic reactions involving inorganic or organic species. Taken together, these structural and functional features suggest that soft porous biomolecule-based colloids are a plausible photosynthetic model that could be developed towards demonstrating aspects of primitive abiotic cellularity.