gebhart/patrepeval huggingface dataset:
New Hyperbranched Poly(siloxysilanes):  Variation of the Branching Pattern and End-Functionalization (1998)

The synthesis of new poly(siloxysilanes) by polyhydrosilation of AB2, AB4, and AB6 monomers using a solid-supported catalyst is described. Analysis of the polymers by gel permeation chromatography shows weight-average molecular weight values near 5−10 000 amu with polydispersities of ∼2. Addition of fresh monomer to the polymerized material only leads to a slight increase in molecular weight. In all cases, polymerization is accompanied by significant intramolecular cyclization side reaction. These results can be explained by considering factors such as the unequal reactivity of the different oligomeric species and their tendency to form cyclic species, but no clear evidence for a growth-limiting effect arising from steric crowding could be seen. End capping of the terminal silicon hydride groups by hydrosilation with a variety of reagents has been demonstrated, affording a diversity of functionalized poly(siloxysilane) materials.
Inhibition of neutral sphingomyelinase-2 facilitates remyelination (2019)

Abstract For reasons that are not completely understood, remyelination is often incomplete, producing thin myelin sheaths with disorganized structure. We investigated the cellular basis for this altered myelin structure, and found that the response of oligodendrocyte progenitor cells (OPCs), and mature oligodendrocytes to TNFα and IL-1β is modified by the expression of the sphingomyelin hydrolase nSMase2. OPCs do not express nSMase2, and exhibit a protective response to these cytokines manifest by decreased ceramide, increased sphingosine 1-phosphate, and increased cell motility. Mature oligodendrocytes express nSMase2, and respond to TNFα and IL-1β with a stress phenotype, evidenced by increased ceramide, decreased sphingosine, and active caspase 3. Pharmacological inhibition or a targeted genetic deletion of nSMase2 in vivo increased myelin thickness, and enhanced myelin compaction. These results suggest that inhibition of nSMase2 improves the quality of new myelin by protecting maturing/myelinating oligodendrocytes. Pharmacological inhibition of nSMase2 following a demyelinating event could stabilize the structure of these newly formed myelin sheaths and protect them from secondary demyelination.
Systems Biology (2009)

Biophysical models have been used in biology for decades, but they have been limited in scope and size. In this book, Bernhard Ø. Palsson shows how network reconstructions that are based on genomic and bibliomic data, and take the form of established stoichiometric matrices, can be converted into dynamic models using metabolomic and fluxomic data. The Mass Action Stoichiometric Simulation (MASS) procedure can be used for any cellular process for which data is available and allows a scalable step-by-step approach to the practical construction of network models. Specifically, it can treat integrated processes that need explicit accounting of small molecules and protein, which allows simulation at the molecular level. The material has been class-tested by the author at both the undergraduate and graduate level. All computations in the text are available online in MATLAB® and Mathematica® workbooks, allowing hands-on practice with the material.
0215 Considerations on experimental results of high-speed lithium wall film flows for the neutron source in Boron Neutron Capture Therapy (BNCT) (2015)

ToThe stability of high-speed liquid lithium film flows on a wall was analytically studied for the neutron source in Boron Neutron Capture Therapy (BNCT), which makes cancers and tumors curable with cell-level selections and hence high QOL. The object of our research is to materialize the thin and high-speed wall film flows of liquid lithium in a high-vacuum as an accelerator target. Linear analysis approach is made to the stability on thin film flows of liquid lithium in a high-vacuum. We experimentally observed the splitting phenomena of film flows on a wall with 0.5 mm in film thickness and over 10.0 m/s in flow velocity, caused by the slit-nozzle was stopped up with the contaminant particulate of nitrous lithium. We also obtained the knowledge to materialize the desired wall film flows.
Highly efficient refractive Gaussian-to-tophat beam shaper for compact terahertz imager (2010)

We describe an efficient and compact terahertz (THz) illumination system as part of an active THz imager. The design and fabrication methods are verified by comparing measurements with wave optical simulations that form a basis for the design of a Gaussian-to-tophat beam shaper. Introducing realistic alignment tolerances in the simulations led to an improved agreement with the experimental data. Furthermore, we propose a method to reduce the alignment effort for THz beam shaping elements by correlating measured results with simulated data of a misaligned system.
Biocatalytic Microcontact Printing (2007)

Immobilized biocatalytic lithography is presented as an application of soft lithography. In traditional microcontact printing, diffusion limits resolution of pattern transfer. By using an immobilized catalyst, the lateral resolution of microcontact printing would depend only on the length and flexibility of the tether (<2 nm) as opposed to diffusion (>100 nm). In the work, exonuclease reversibly immobilized on a relief-patterned stamp is used to ablate ssDNA monolayers Percent of ablation was determined via confocal fluorescence microscopy to be approximately 70%.
Fabrication of Optical Nano-Hairs for High Power Applications (2013)

The method of calculating the dose of radioiodine (fixed <i>vs</i>. individualized) to treat feline hyperthyroidism does not appear to be decisive for posttreatment thyroid function, renal function, or survival.
MEMS capacitive series switches: optimal test vehicles for the RF self-biasing phenomenon (2005)

This paper demonstrates the use of the cantilever series capacitive RF-MEMS switches to study qualitatively the RF self-biasing. These devices are less prone to RF Joule heating than the commonly used bridge shunt switches and exhibit the same self-actuation phenomena but at lower power levels and at lower frequencies. Therefore, series switches provide a much better test/study vehicle for this complex problem. Some new findings are the existence of the non-zero pull-out power and its dependence on the frequency, the increase or decrease of pull-in power with the frequency depending on the device characteristic, the closure of the instability window for the air gap height and the consequent full tuning range. Our model was validated with original measurements focusing on the frequency dependence of the RF self-actuation characteristics. This approach allows using a single structure to realize a qualitative verification of various phenomena predicted by our model.
Modeling and Analysis of the Role of Energy Storage for Renewable Integration: Power Balancing (2013)

The high variability of renewable energy is a major obstacle toward its increased penetration. Energy storage can help reduce the power imbalance due to the mismatch between the available renewable power and the load. How much can storage reduce this power imbalance? How much storage is needed to achieve this reduction? This paper presents a simple analytic model that leads to some answers to these questions. Considering the multitimescale grid operation, we formulate the power imbalance problem for each timescale as an infinite horizon stochastic control problem and show that a greedy policy minimizes the average magnitude of the residual power imbalance. Observing from the wind power data that in shorter timescales the power imbalance can be modeled as an iid zero-mean Laplace distributed process, we obtain closed form expressions for the minimum cost and the stationary distribution of the stored power. We show that most of the reduction in the power imbalance can be achieved with relatively small storage capacity. In longer timescales, the correlation in the power imbalance cannot be ignored. As such, we relax the iid assumption to a weakly dependent stationary process and quantify the limit on the minimum cost for arbitrarily large storage capacity.
Dynamic Stereoselection of Peptide Helicates and Their Selective Labeling of DNA Replication Foci in Cells (2020)

Peptide engineering has been extremely successful in creating new structures with defined properties and functions. Although generally overlooked in this context, coordination chemistry offers an additional set of interactions that opens unexplored design opportunities for developing complex molecular structures. With this in mind, we report the development of new artificial peptide ligands that fold into chiral and discrete supramolecular helicates in the presence of labile metal ions such as Fe(II) and Co(II). By selecting appropriate heterochiral β‑turn promoting sequences, we can encode the stereoselective folding of the peptide ligand, and define the physicochemical properties of their corresponding metal complexes. The study of these metallopeptides by CD and NMR spectroscopy, combined with computational methods allowed us to identify and determine the structure of two isochiral ΛΛ-helicates, folded as topological isomers. We also show that these new peptide helicates, dynamically selected in the presence of labile Co(II) ions, can be locked as kinetically-inert species by in situ oxidation to Co(III). Finally, in addition to the in vitro characterization of their selective binding to three-way DNA, cell microscopy experiments demonstrated that a rhodamine-labeled Fe(II) helicate was internalized and selectively stains DNA replication factories in functional cells.
Deep sequencing and pathway-focused analysis revealed multigene oncodriver signatures predicting survival outcomes in advanced colorectal cancer (2018)

Genomic technologies are reshaping the molecular landscape of colorectal cancer (CRC), revealing that oncogenic driver mutations (APC and TP53) coexist with still underappreciated genetic events. We hypothesized that mutational analysis of CRC-linked genes may provide novel information on the connection between genetically-deregulated pathways and clinical outcomes. We performed next-generation sequencing (NGS) analysis of 16 recurrently mutated genes in CRC exploiting tissue specimens from 98 advanced CRC patients. Multiple correspondence analysis (MCA) was used to identify gene sets characterizing negative and positive outliers (patients in the lowest and highest quartile of progression-free survival, PFS). Variables potentially affecting PFS and overall survival (OS) were tested in univariate and multivariate Cox proportional hazard models. Sensitivity analyses and resampling were used to assess the robustness of genomic predictors. MCA revealed that APC and TP53 mutations were close to the negative outlier group, whereas mutations in other WNT pathway genes were in proximity of the positive outliers. Reasoning that genetic alterations interact epistatically, producing greater or weaker consequences in combination than when individually considered, we tested whether patients whose tumors carried a genetic background characterized by APC and TP53 mutations without coexisting mutations in other WNT genes (AMER1, FBXW7, TCF7L2, CTNNB1, SOX9) had adverse survival outcomes. With this approach, we identified two oncodriver signatures (ODS1 and ODS2) associated with shorter PFS (ODS1 multivariate Cox for PFS: HR 2.16, 95%CI: 1.28-3.64, p = 0.004; ODS2 multivariate Cox for PFS: HR 2.61, 95%CI: 1.49-4.58, p = 0.001). Clinically-focused and molecularly-focused sensitivity analyses, resampling, and reclassification of mutations confirmed the stability of ODS1/2. Moreover, ODS1/2 negatively impacted OS. Collectively, our results point to co-occurring driver mutations as an adverse molecular factor in advanced CRC. This relationship depends on a broader genetic context highlighting the importance of genetic interactions.
Influence of ion energy and substrate temperature on the optical and electronic properties of tetrahedral amorphous carbon (ta-C) films (1997)

The properties of amorphous carbon (a-C) deposited using a filtered cathodic vacuum arc as a function of the ion energy and substrate temperature are reported. The sp3 fraction was found to strongly depend on the ion energy, giving a highly sp3 bonded a-C denoted as tetrahedral amorphous carbon (ta-C) at ion energies around 100 eV. The optical band gap was found to follow similar trends to other diamondlike carbon films, varying almost linearly with sp2 fraction. The dependence of the electronic properties are discussed in terms of models of the electronic structure of a-C. The structure of ta-C was also strongly dependent on the deposition temperature, changing sharply to sp2 above a transition temperature, T1, of ≈200 °C. Furthermore, T1 was found to decrease with increasing ion energy. Most film properties, such as compressive stress and plasmon energy, were correlated to the sp3 fraction. However, the optical and electrical properties were found to undergo a more gradual transition with the deposition temperature which we attribute to the medium range order of sp2 sites. We attribute the variation in film properties with the deposition temperature to diffusion of interstitials to the surface above T1 due to thermal activation, leading to the relaxation of density in context of a growth model.
c-Jun N-Terminal Kinase 1 Phosphorylates Myt1 To Prevent UVA-Induced Skin Cancer (2009)

The c-Jun N-terminal kinase (JNK) signaling pathway is known to mediate both survival and apoptosis of tumor cells. Although JNK1 and JNK2 have been shown to differentially regulate the development of skin cancer, the underlying mechanistic basis remains unclear. Here, we demonstrate that JNK1, but not JNK2, interacts with and phosphorylates Myt1 ex vivo and in vitro. UVA induces substantial apoptosis in JNK wild-type (JNK(+/+)) or JNK2-deficient (JNK2(-/-)) mouse embryonic fibroblasts but has no effect on JNK1-deficient (JNK1(-/-)) cells. In addition, UVA-induced caspase-3 cleavage and DNA fragmentation were suppressed by the knockdown of human Myt1 in skin cancer cells. JNK1 deficiency results in suppressed Myt1 phosphorylation and caspase-3 cleavage in skin exposed to UVA irradiation. In contrast, the absence of JNK2 induces Myt1 phosphorylation and caspase-3 cleavage in skin exposed to UVA. The overexpression of JNK1 with Myt1 promotes cellular apoptosis during the early embryonic development of Xenopus laevis, whereas the presence of JNK2 reduces the phenotype of Myt1-induced apoptotic cell death. Most importantly, JNK1(-/-) mice developed more UVA-induced papillomas than either JNK(+/+) or JNK2(-/-) mice, which was associated with suppressed Myt1 phosphorylation and decreased caspase-3 cleavage. Taken together, these data provide mechanistic insights into the distinct roles of the different JNK isoforms, specifically suggesting that the JNK1-mediated phosphorylation of Myt1 plays an important role in UVA-induced apoptosis and the prevention of skin carcinogenesis.
Aerosol Synthesis of Inhalation Particles via a Droplet-to-Particle Method (2006)

ABSTRACT Inhalation powders with consistent particle properties, including particle size, size distribution, and shape were produced with an aerosol synthesis method. Compared to conventional spray drying, the aerosol method provides better control of the thermal history and residence time of each droplet and product particle due to the laminar flow in the heated zone of the reactor where the droplet drying and particle formation take place. A corticosteroid, beclomethasone dipropionate, generally used for asthma treatment was chosen as a representative material to demonstrate the process. Spherical particles were produced with a droplet-to-particle method from an ethanolic precursor solution. The droplets produced with an ultrasonic nebulizer were carried to a heated zone of the reactor at 50–150°C where the solvent was evaporated and dry particles formed. The mass mean diameter of the particles were well within the respirable size range (approximately 2 μm). The geometric standard deviation (GSD) of produced particles was approximately 2. The particle surface structure varied from smooth to rough depending on the degree of particle crystallinity and was affected by the thermal history of the particle. Amorphous particles with smooth surface were most likely obtained due to the rapid evaporation of the solvent from the droplet combined with the slow diffusion of the beclomethasone dipropionate molecule. The amorphous particles were transformed slowly to crystalline particles in the open atmosphere. In addition, the particle surface structure changed from smooth to rough during storage. The process was accelerated by thermal post-annealing. However, additional heating also increased particle sintering. By optimizing the reactor parameters, and thus increasing the molecular diffusion, stable, crystalline particles were produced at 150°C.
Incoherent noise and quantum information processing (2004)

Incoherence in the controlled Hamiltonian is an important limitation on the precision of coherent control in quantum information processing. Incoherence can typically be modeled as a distribution of unitary processes arising from slowly varying experimental parameters. We show how it introduces artifacts in quantum process tomography and we explain how the resulting estimate of the superoperator may not be completely positive. We then go on to attack the inverse problem of extracting an effective distribution of unitaries that characterizes the incoherence via a perturbation theory analysis of the superoperator eigenvalue spectra.
A heavy traffic approach for queue-aware power control in interfering wireless links (2012)

In this work, we address the problem of power allocation for interfering transmitter-receiver pairs so that the probability that each queue length exceeds a specified threshold is fixed at a desired value. One application is satisfying QoS requirements in a dense cellular network. We address this problem using heavy traffic approximation techniques which lead to an asymptotic model described by a (controlled) stochastic differential equation. The power control strategy consists in allocating most of the power according to the wireless channel state and a smaller fraction according to the queue lengths. Simulation results in a simple setting illustrate that the proposed control policy can yield desirable results in practical systems.
Zinc oxide nanowires and nanorods fabricated by vapour-phase transport at low temperature (2004)

Using zinc chloride as source material, zinc oxide nanowires and nanorods were fabricated by a vapour-phase transport method at low temperature. The nanowires grown on gold-coated silicon showed a uniform diameter of about 40 nm, and the nanorods on copper-coated silicon grew upwards to form flower-like arrays. The x-ray diffraction and transmission electron microscopy analyses demonstrated that the nanostructural zinc oxide grew along the [0001] direction. The growth process was attributed to a vapour-liquid-solid mechanism. Distinct photoluminescent behaviours were observed for zinc oxide nanostructures grown on gold-coated and copper-coated silicon wafers.
Repurposing the Ebola and Marburg Virus Inhibitors Tilorone, Quinacrine, and Pyronaridine: In Vitro Activity against SARS-CoV-2 and Potential Mechanisms (2021)

Severe acute respiratory coronavirus 2 (SARS-CoV-2) is a newly identified virus that has resulted in over 2.5 million deaths globally and over 116 million cases globally in March, 2021. Small-molecule inhibitors that reverse disease severity have proven difficult to discover. One of the key approaches that has been widely applied in an effort to speed up the translation of drugs is drug repurposing. A few drugs have shown in vitro activity against Ebola viruses and demonstrated activity against SARS-CoV-2 in vivo. Most notably, the RNA polymerase targeting remdesivir demonstrated activity in vitro and efficacy in the early stage of the disease in humans. Testing other small-molecule drugs that are active against Ebola viruses (EBOVs) would appear a reasonable strategy to evaluate their potential for SARS-CoV-2. We have previously repurposed pyronaridine, tilorone, and quinacrine (from malaria, influenza, and antiprotozoal uses, respectively) as inhibitors of Ebola and Marburg viruses in vitro in HeLa cells and mouse-adapted EBOV in mice in vivo. We have now tested these three drugs in various cell lines (VeroE6, Vero76, Caco-2, Calu-3, A549-ACE2, HUH-7, and monocytes) infected with SARS-CoV-2 as well as other viruses (including MHV and HCoV 229E). The compilation of these results indicated considerable variability in antiviral activity observed across cell lines. We found that tilorone and pyronaridine inhibited the virus replication in A549-ACE2 cells with IC50 values of 180 nM and IC50 198 nM, respectively. We used microscale thermophoresis to test the binding of these molecules to the spike protein, and tilorone and pyronaridine bind to the spike receptor binding domain protein with Kd values of 339 and 647 nM, respectively. Human Cmax for pyronaridine and quinacrine is greater than the IC50 observed in A549-ACE2 cells. We also provide novel insights into the mechanism of these compounds which is likely lysosomotropic.
A novel CT perfusion protocol for quantitative contrast material mapping (2009)

In conventional CT-assisted perfusion imaging the quantitative assessment of diagnostically important parameters (e.g. cerebral blood flow and cerebral blood volume for brain perfusion) is based on the CT numbers in the acquired images. These CT numbers are distorted by a number of artifacts, especially by beam hardening. The distortion due to beam hardening can be avoided by acquiring the first images after injection of the contrast agent with a dual kV-scan, and decompose the projections into base component line integrals representing Compton scattering and photo effect. These base component line integrals can be used to estimate the contrast material line integrals from the projections of the following CT scans, done in a conventional manner. The contrast material line integrals can then be reconstructed to get a quantitative iodine map, from which perfusion parameters can be calculated more accurately. Based on simulated data, we show that this technique indeed has the potential to completely eliminate errors in the estimation of perfusion parameters due to beam hardening.
Molecular Basis for Regulation of Mammalian Fatty Acid Synthase (2022)

De novo lipogenesis (DNL) is an essential metabolic process that converts excess cellular glucose to fatty acids. Fatty Acid Synthase (FASN) is a key enzyme in the DNL pathway and has shown promising pre‐clinical results as a therapeutic target in a variety of metabolic diseases, including cancer, non‐alcoholic fatty liver disease (NAFLD), and most recently COVID‐19. Mammalian FASN is a large multifunctional enzyme with 6 catalytic domains and a flexibly tethered acyl carrier protein (ACP). The ACP shuttles covalently linked intermediates between catalytic domains to facilitate palmitate synthesis. Previous negative stain electron microscopy data has shown that mammalian FASN is a dynamic enzyme that adopts multiple conformations in solution, but the role of these conformational dynamics in the mechanism of FASN is yet to be determined. To understand how the conformational dynamics of mammalian FASN contribute to the overall mechanism and its’ regulation, we have generated multiple constructs and characterized their enzymatic activity using diverse biochemical assays. Additionally, we have made progress towards understanding the enzyme dynamics using Hydrogen‐Deuterium Exchange Mass Spectrometry (HDX‐MS). We are actively pursuing structural studies to implement an integrative approach towards advancing our understanding of the complex mechanism of mammalian FASN.