gebhart/patrepeval huggingface dataset:
TRPV1 Gates Tissue Access and Sustains Pathogenicity in Autoimmune Encephalitis (2013)

Multiple sclerosis (MS) is a chronic progressive, demyelinating condition whose therapeutic needs are unmet, and whose pathoetiology is elusive. We report that transient receptor potential vanilloid-1 (TRPV1) expressed in a major sensory neuron subset, controls severity and progression of experimental autoimmune encephalomyelitis (EAE) in mice and likely in primary progressive MS. TRPV1-/- B6 congenics are protected from EAE. Increased survival reflects reduced central nervous systems (CNS) infiltration, despite indistinguishable T cell autoreactivity and pathogenicity in the periphery of TRPV1-sufficient and -deficient mice. The TRPV1+ neurovascular complex defining the blood-CNS barriers promoted invasion of pathogenic lymphocytes without the contribution of TRPV1-dependent neuropeptides such as substance P. In MS patients, we found a selective risk-association of the missense rs877610 TRPV1 single nucleotide polymorphism (SNP) in primary progressive disease. Our findings indicate that TRPV1 is a critical disease modifier in EAE, and we identify a predictor of severe disease course and a novel target for MS therapy.
Mass determination of thin biological specimens for use in quantitative electron probe X-ray microanalysis. (1982)

In the quantitative electron probe X-ray microanalysis of thin specimens the total mass thickness of a specimen is often required to express the elemental content as fractions of the total mass. In the present paper three methods for the measurement of mass thickness of thin specimens are reviewed and compared as to their applicability for use in quantitative X-ray microanalysis. The methods are based on the use of the continuum X-ray intensity, the backscattered electron intensity, and the transmitted electron intensity, respectively. From experimental results, it is concluded that the mass measurement method, based on the transmitted electron intensity, gives more accurate mass values than does the continuum X-ray method. The use of an independent mass measurement method is advantageous when low temperature oxygen plasma ashing is applied to lower X-ray analysis detection limits. In this way, elements present in ashed specimens can be expressed as fractions of the original specimen mass.
Propene Epoxidation with H2/H2O/O2 Mixtures Over Gold Atoms Supported on Defective Graphene: A Theoretical Study (2012)

The mechanism of propene epoxidation by H2/H2O/O2 mixtures catalyzed by gold atoms supported on defective graphene has been investigated by means of periodic density functional theory (DFT) calculations. The fact of being isolated and yet strongly bound to the support gold atoms makes formation of gold hydroperoxide H–Au–OOH intermediates from H2 and O2 barrierless and the subsequent reaction with propene yielding propene oxide (PO) and H2O thermodynamically and kinetically favored. The main advantage of the Au/graphene material explored in this work is not related to catalyst activity but to the selectivity toward PO that is greatly enhanced due to suppression of the main competing routes. Thus, neither propene hydrogenation yielding propane nor O2 dissociation finally resulting in acrolein formation and/or propene combustion can compete with the desired epoxidation. The present results suggest a promising route to prepare active and highly selective gold-based catalysts for propene epoxidation
System-architectures for sensor networks issues, alternatives, and directions (2003)

Our goal is to identify the key architectural and design issues related to Sensor Networks (SNs), evaluate the proposed solutions, and to outline the most challenging research directions. The evaluation has three scopes ndividual components on SN nodes (processor, communication, storage, sensors, actuators, and power supply), node level and networked system level. The special emphasis is placed on architecture and system software, and on new challenges related to the usage of new types of components in networked systems. The evaluation is guided by anticipated technology trends and both current and future applications. The main conclusion of the analysis is that the architectural and synthesis emphasis will be shifted from computation and to some extent communication components to sensors and actuators.
Edema, Oncotic Pressure, and Free Entropy: Novel Considerations for the Treatment of Edema through Attention to Thermodynamics (1998)

Over 170 years after Richard Bright and a century after Ernest H. Starling, the development, location, and severity of edema in patients with renal impairment continue to baffle the predictions of most nephrologists. While much of the phenomenon can be explained by levels of serum proteins, or hydrostatic pressures, there are stunning exceptions well known to any practicing nephrologist. Some of the derangement is undoubtedly due to unmeasured but well-known variables, such as membrane permeability; however, other factors such as free entropy of plasma are also clearly involved. The study of other polyelectrolyte colloids, similar to plasma proteins, for industrial purposes has led to the identification of various phenomena such as counterion condensation that can result in loss of entropy and consequently osmotic pressure. Variables known to result in a loss of free entropy, such as pH, oxidation products and ligand binding, are discussed. Older equations developed by van't Hoff and Donnan might require replacement by newer mathematical models such as the nonlinear Poisson-Boltzmann equation or the Monte Carlo simulator. Attempts to restore free entropy to plasma would be a more physiological treatment of edema than diuretic use. Implications are noted for future drug development to treat edema.
High Throughput Screening Method for Determination of Equilibrium Drug solubility (2009)

Using a UV platereader, multichannel pipettes and disposable 96-well plates, we have developed a method which allows high throughput screening of the equilibrium solubility of drugs in aqueous media. The method was developed as part of an effort to evaluate the potential of hydroxybutenyl-β-cyclodextrin (HBenCD) for the delivery of poorly soluble drugs. This method differs from other reported high throughput screening methods in that thermodynamic or equilibrium solubility is measured at greatly increased throughput and without the use of an organic solvent. Conservatively a 100 fold increase in test throughput can be achieved. Additionally, a high throughput method for measuring solution stability was developed.
Magnetic characterization of γ-Fe2O3 nanoparticles fabricated by aerosol pyrolysis (1998)

The magnetic properties of γ-Fe2O3 nanoparticles prepared by spray pyrolysis of dilute solutions of Fe(III) and Fe(II) salts have been investigated using both magnetic measurements and Mössbauer spectroscopy. The most outstanding magnetic features are the strong reduction of the saturation magnetization compared with that of the bulk material, and the existence of magnetic hysteresis up to the highest field used (55 kOe) in both the M(H) loops and the zero-field cooling-field cooling M(T) curves. The magnetic particles exhibit superparamagnetic behavior at room temperature. From the evolution of the ferromagnetic ratio, MR/MS, with temperature we have determined the distribution of the blocking temperatures that can be described properly with a log–normal distribution, which allows the determination of mean blocking temperatures 〈TB〉 and mean particle volumes.
Pilot-Assisted Channel Estimation Methods for Coherent Receivers (2013)

We analyze time domain and frequency domain channel estimation methods with respect to their accuracy and implementation effort. We investigate the trade-off between training overhead, performance, and tolerance to distortions.
Exabyte helical scan devices at Fermilab (1989)

The Exabyte 8-mm helical-scan storage devices in use at Fermilab in a number of applications are described. These devices have the functionality of magnetic tape but use media that are much more economical and much more dense than conventional 9-track tape. The discussion covers: uses for helical scan tape systems; the initial evaluation of Exabytes; their use in the Fermilab lattice supercomputer project; their use in a VME-based data acquisition system; the problems observed in a VME environment; their use as general-purpose tape drives for VAX/VMS; a copy facility for converting 9-track tapes to 8-mm cartridges and replicating 8-mm tapes for distribution to dispersed experiment collaborators; problems observed under VMS; and diagnostics implemented to reproduce and understand the problems remaining with these devices. >
Surface modification of ZnO nanostructured electrodes with thiol and phosphonic acid moieties for biosensing applications (2017)

The analytical performance of affinity immunoassay based biosensor systems is determined by the efficiency of capture probe immobilization, which in turn depends on the stability of surface modification.
Engineering and Modeling the Electrophoretic Trapping of a Single Protein Inside a Nanopore (2019)

The ability to confine and to study single molecules has enabled important advances in natural and applied sciences. Recently, we have shown that unlabeled proteins can be confined inside the biological nanopore Cytolysin A (ClyA) and conformational changes monitored by ionic current recordings. However, trapping small proteins remains a challenge. Here, we describe a system where steric, electrostatic, electrophoretic, and electro-osmotic forces are exploited to immobilize a small protein, dihydrofolate reductase (DHFR), inside ClyA. Assisted by electrostatic simulations, we show that the dwell time of DHFR inside ClyA can be increased by orders of magnitude (from milliseconds to seconds) by manipulation of the DHFR charge distribution. Further, we describe a physical model that includes a double energy barrier and the main electrophoretic components for trapping DHFR inside the nanopore. Simultaneous fits to the voltage dependence of the dwell times allowed direct estimates of the <i>cis</i> and <i>trans</i> translocation probabilities, the mean dwell time, and the force exerted by the electro-osmotic flow on the protein (≅9 pN at -50 mV) to be retrieved. The observed binding of NADPH to the trapped DHFR molecules suggested that the engineered proteins remained folded and functional inside ClyA. Contact-free confinement of single proteins inside nanopores can be employed for the manipulation and localized delivery of individual proteins and will have further applications in single-molecule analyte sensing and enzymology studies.
Geometric Mistuning Reduced Order Model Development Utilizing Bayesian Surrogate Models for Component Mode Calculations (2019)

Abstract By design, Integrally Bladed Rotors (IBRs) are meant to be tuned, rotationally periodic structures. However, unique variations in geometries and material properties from sector-to-sector, referred to as mistuning, destroy the structural periodicity. This results in mode localization that can induce forced response levels greater than what is predicted with a tuned-structure analysis. Furthermore, mistuning and mode localization are random processes that require stochastic treatments when analyzing the distribution of fleet responses. Generating this distribution can be computationally intensive when using the full finite element model. To overcome this expense, Reduced Order Models (ROMs) have been developed to accommodate fast calculations of mistuned forced response levels for a fleet of random IBRs. Usually, ROMs can be classified by two main families: frequency-based and geometry-based methods. Frequency-based ROMs assume mode shapes do not change due to mistuning. However, this assumption has been shown to cause errors that propagate to the fleet distribution. To circumvent these errors, geometry-based ROMs have been developed to provide accurate predictions. However, these methods require recalculating modal data during ROM formulations. This increases the computational expense in computing fleet distributions. A new geometry-based ROM is presented to reduce this cost. The developed ROM utilizes a Bayesian surrogate model in place of sector modal calculations required in ROM formulations. This method, referred to as the Surrogate Modal Analysis for Geometry Mistuning Assessments (SMAGMA), will propagate the uncertainties of the surrogate prediction to the forced response. Assessments of the ROM accuracy are made by comparing results to the true forced response levels and results computed by a frequency-based ROM.
Data from Ras/Raf-1/MAPK Pathway Mediates Response to Tamoxifen but not Chemotherapy in Breast Cancer Patients (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; The expression and activation of the Ras/Raf-1/mitogen-activated protein kinase (MAPK) pathway plays an important role in the development and progression of cancer, and may influence response to treatments such as tamoxifen and chemotherapy. In this study we investigated whether the expression and activation of the key components of this pathway influenced clinical outcome, to test the hypothesis that activation of the MAPK pathway drives resistance to tamoxifen and chemotherapy in women with breast cancer.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Breast tumors from patients at the Glasgow Royal Infirmary and others treated within the BR9601 trial were analyzed for expression of the three Ras isoforms, total Raf-1, active and inactive forms of Raf-1 [pRaf(ser338) and pRaf(ser259), respectively], MAPK, and phospho-MAPK using an immunohistochemical approach. Analyses were done with respect to disease free-survival and overall survival.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Expression and activation of the Ras pathway was associated with loss of benefit from treatment with tamoxifen but not chemotherapy. Overexpression of pRaf(ser338) was associated with shortened disease-free and overall survival time in univariate analyses. Multivariate analysis suggested pRaf(ser338) was independent of known prognostic markers in predicting outcome following tamoxifen treatment (&lt;i&gt;P&lt;/i&gt; = 0.03).&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; This study suggests that activation of the Ras pathway predicts for poor outcome on tamoxifen but not chemotherapy, and identifies pRaf(ser338) as a potential marker of resistance to estrogen receptor–targeted therapy. In addition, it suggests that expression of pRaf(ser338) could identify patients for whom tamoxifen alone is insufficient adjuvant systemic therapy, but for whom the addition of chemotherapy may be of benefit.&lt;/p&gt;&lt;/div&gt;
Data from <i>ETV6</i> Deficiency Unlocks ERG-Dependent Microsatellite Enhancers to Drive Aberrant Gene Activation in B-Lymphoblastic Leukemia (2023)

&lt;div&gt;Abstract&lt;p&gt;Distal enhancers play critical roles in sustaining oncogenic gene-expression programs. We identify aberrant enhancer-like activation of GGAA tandem repeats as a characteristic feature of B-cell acute lymphoblastic leukemia (B-ALL) with genetic defects of the &lt;i&gt;ETV6&lt;/i&gt; transcriptional repressor, including &lt;i&gt;ETV6–RUNX1&lt;/i&gt;&lt;sup&gt;+&lt;/sup&gt; and &lt;i&gt;ETV6&lt;/i&gt;-null B-ALL. We show that GGAA repeat enhancers are direct activators of previously identified &lt;i&gt;ETV6–RUNX1&lt;/i&gt;&lt;sup&gt;+/−&lt;/sup&gt; like B-ALL “signature” genes, including the likely leukemogenic driver &lt;i&gt;EPOR&lt;/i&gt;. When restored to ETV6-deficient B-ALL cells, ETV6 directly binds to GGAA repeat enhancers, represses their acetylation, downregulates adjacent genes, and inhibits B-ALL growth. In ETV6-deficient B-ALL cells, we find that the ETS transcription factor ERG directly binds to GGAA microsatellite enhancers and is required for sustained activation of repeat enhancer-activated genes. Together, our findings reveal an epigenetic gatekeeper function of the &lt;i&gt;ETV6&lt;/i&gt; tumor suppressor gene and establish microsatellite enhancers as a key mechanism underlying the unique gene-expression program of &lt;i&gt;ETV6–RUNX1&lt;/i&gt;&lt;sup&gt;+/−&lt;/sup&gt; like B-ALL.&lt;/p&gt;Significance:&lt;p&gt;We find a unifying mechanism underlying a leukemia subtype-defining gene-expression signature that relies on repetitive elements with poor conservation between humans and rodents. The ability of ETV6 to antagonize promiscuous, nonphysiologic ERG activity may shed light on other roles of these key regulators in hematolymphoid development and human disease.&lt;/p&gt;&lt;p&gt;&lt;i&gt;&lt;a href="https://aacrjournals.org/bloodcancerdiscov/article/doi/10.1158/2643-3230.BCD-22-0177" target="_blank"&gt;See related commentary by Mercher, p. 2.&lt;/a&gt;&lt;/i&gt;&lt;/p&gt;&lt;p&gt;&lt;i&gt;&lt;a href="https://aacrjournals.org/bloodcancerdiscov/article/doi/10.1158/2643-3230.BCD-4-1-ITI" target="_blank"&gt;This article is highlighted in the In This Issue feature, p. 1&lt;/a&gt;&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
Low-Voltage Limitations and Challenges of Memory-Rich Nano-Scale CMOS LSIs (2007)

A major challenge to nano-scale CMOS LSIs comprising a large RAM (SRAM or DRAM) block and a logic block is to reduce the minimum operation voltage VDD (Vmin) to the deep-sub-1-V region. However, this is becoming extremely difficult to do in conventional bulk CMOS LSIs as devices and voltages are scaled down. On the contrary, Vmin must be increased, resulting in intolerable increases in power dissipation and internal supply-voltage noise, and degraded device reliability with increase stress voltage. The un-scalable feature of the lowest-necessary VT(VTO) of MOSFETs to keep the subthreshold current low, and the ever-increasing VT variation are responsible for the increase. In particular, the VT variation calls for increasing Vmin to offset increases in speed (delay) variations of circuits, degradation of voltage margins of flip-flops such as SRAM cells and DRAM sense amplifiers, as well as soft-error rate (SER) of RAM cells and even logic gates. Although clarifying and solving the ever-increasing Vmin problem is extremely important and urgent to extend CMOS scaling, to my knowledge, there has been no paper describing the problem systematically and consistently from the view point of circuit designers. This is the case especially for the VT variation issue although it came to light as early as 1994. In this talk, a new evaluation methodology of Vmin is proposed, and the low-voltage-limitation problem and possible solutions for memory-rich deep-sub-100-nm CMOS LSIs are described, putting an emphasis on the VT variation.
Porphyrin based metal-organic frameworks with record sensitivity in optical oxygen sensing (2021)

The optical oxygen sensing capabilities of the porphyrin-based metal-organic frameworks, PCN-224, Pt(II)PCN-224 and Pd(II)PCN-224 were investigated. The bimolecular quenching constants (kq) of 37000 (PCN-224), 6700 (Pd(II)PCN-224) and 3900 Pa-1s-1 (Pt(II)PCN-224) were found and reveal an exceptionally high oxygen-permeability for these materials. A fast gas transport within the network, large pore sizes, electronic and spatial isolation of the porphyrin indicator in the framework are held responsible for the unprecedentedly high kq values. PCN-224 shows 6.7 ns fluorescence lifetime and the fluorescence in air is quenched by 4.2-fold. The metal-organic frameworks based on phosphorescent Pt(II) and Pd(II) porphyrins possess significantly longer decay times of 18.6 and 390 µs, respectively, and are suited to detect oxygen in trace and ultra-trace ranges with limits of detection of 1 and 0.015 Pa, respectively. Apart from free-standing crystals, also metal-organic frameworks supported on different fibrous substrates (poly(acrylonitrile) nanofibers, glass fibres), and flat substrates (TLC silica-gel, poly(amide) filter) were prepared in order to provide oxygen sensor materials of practical use. Electrospun and thermally treated poly(acrylonitrile) nanofibers were proven to be particularly favourable and the resulting composite material exhibited the same sensitivity as the free crystals. All sensing materials show reversible cross-talk to humidity at levels up to 53 % relative humidity but demonstrate a drastic decrease of oxygen sensitivity at high humidity levels and when exposed to water.
Supplementary Figures 1-3 from Frequent Inactivation of <i>Cysteine Dioxygenase Type 1</i> Contributes to Survival of Breast Cancer Cells and Resistance to Anthracyclines (2023)

&lt;p&gt;PDF File - 383K, Supplementary Figure 1 displays genomic location, structure and CpG island of the CDO1 gene.&lt;/p&gt;
Global Optimization and Deep Learning Techniques For Freeform Nanophotonic Metadevices (2023)

Engineered freeform components are advancing the state of the art in the field of nanophotonics. To this end, optical metasurfaces are increasingly desirable due to their ability to control the phase, magnitude, and polarization of transmitted (and/or reflected) light and improvements in nanofabrication techniques. While metasurfaces have demonstrated unprecedented control over optical performances, it is not well understood how to determine the geometries necessary to achieve a targeted optical performance. That being so, optimization and inverse-design techniques have proven invaluable to engineers seeking to realize metadevices with specific targeted functionalities. In this presentation, we discuss the advantages of our metadevice design process which utilizes a combination of global optimization and deep learning to realize an accelerated mutliobjective framework for generating highly performant designs that are robust to fabrication uncertainties.
Separation of quantitation of intracellular forms of poliovirus RNA by agarose gel electrophoresis (1977)

Intracellular poliovirus-specific RNA species can be measured directly by electrophoresis of total cytoplasmic nucleic acids through 1% agarose gels, resulting in the separation of single- and double-stranded forms of poliovirus RNA from each other and from HeLa cell 28S ribosomal RNA. Single-stranded RNA molecules differing by only 15% in length are resolved in this gel system. RNA species can be visualized as fluorescen bands appearing after staining of the gels with ethidium bromide and observation under ultraviolet illumination. The total amount of RNA can be determined by densitometric quantitation of the fluorescent response. In this way, the amount of poliovirus-specific RNA within the cytoplasm of HeLa cells infected for various times has been estimated. At 170-min postinfection, there are 0.67 X 10(5) molecules of single-stranded poliovirus RNA per cell and at 230 min, the amount has increased to 3.7 X 10(5) molecules/cell. Poliovirus double-strnaded RNA reaches a maximum of 0.7 X 10(5) molecules/cell at 330 min after infection.
Design and Synthesis of Imidazopyrazolopyridines as Novel Selective COX-2 Inhibitors (2015)

The usefulness of non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by their gastrointestinal side effects. Non-selective cyclooxygenases inhibitors interfere with both COX-1 and COX-2 isozymes. Since COX-1 mediates cytoprotection of gastric mucosa, its inhibition leads to the undesirable side effects. On the other hand, COX-2 is undetectable in normal tissues and selectively induced by inflammatory stimuli. Therefore, it is strongly believed that the therapeutic benefits derive from inhibition of COX-2 only. The presence of a strong connection between reported COX-2 inhibitors and cardiac toxicity encourages medicinal chemists to explore new scaffolds. In the present study, we introduced imidazopyrazolopyridines as new potent and selective COX-2 inhibitors that lack the standard pharmacophoric binding features to hERG. Starting from our lead compound 5a, structure-based drug-design was conducted and more potent analogues were obtained with high COX-2 selectivity and almost full edema protection, in carrageenan-induced edema assay, in case of compound 5e. Increased bulkiness around imidazopyrazolopyridines by adding a substituted phenyl ring(s) afforded less active compounds.