gebhart/patrepeval huggingface dataset:
Supplementary Figure 3I from Aberrant Silencing of Cancer-Related Genes by CpG Hypermethylation Occurs Independently of Their Spatial Organization in the Nucleus (2023)

Supplementary Figure 3I from Aberrant Silencing of Cancer-Related Genes by CpG Hypermethylation Occurs Independently of Their Spatial Organization in the Nucleus
Double Diffraction in the Fresnel Region (1971)

Double diffraction pattern of two identical gratings placed in the Fresnel region is sensitive to the relative displacement of the gratings, and this phenomenon can be used as a method of displacement measurement. Experimental studies and computer analyses on the contrast revealed that a very high contrast (over 90% modulation depth) can be obtained for the zeroth order beam when the separation of the gratings satisfy the Fourier image conditions. The contrast is also affected by the finite radius of coherent component of the incident laser beam, which was shown by the simultaneous measurement of the spatial coherence factor of the source.
ADAM17 but Not ADAM10 Mediates Tumor Necrosis Factor-α and L-Selectin Shedding from Leukocyte Membranes (2001)

The release of tumor necrosis factor-alpha (TNF-alpha) from cellular membranes has been shown by different laboratories to be controlled by a disintegrin and metalloprotease, ADAM10 or ADAM17. In contrast, only ADAM17 has shown to be involved in L-selectin shedding. To determine the specific roles of ADAM10 and ADAM17 in the processing of TNF-alpha and L-selectin shedding, antisense oligonucleotides (ASO) targeting both ADAM10 and ADAM17 were identified. We show that ISIS 16337 reduces ADAM17 mRNA and ISIS 100750 reduces ADAM10 mRNA in a sequence-specific and dose-dependent manner in both Jurkat and THP-1 cells. The ADAM17 ASO (ISIS 16337) inhibited both TNF-alpha secretion in THP-1 cells and L-selectin shedding in Jurkat cells, whereas the ADAM10 ASO (ISIS 100750) did not significantly inhibit release of either protein. These results suggest that ADAM17 is one of the major metalloproteases involved in L-selectin shedding as well as TNF-alpha processing. The biologic substrates for ADAM10 in Jurkat and THP-1 cells remain to be elucidated.
Structural and Inhibition Analysis Reveals the Mechanism of Selectivity of a Series of Aggrecanase Inhibitors (2009)

Several inhibitors of a series of cis-1(S)2(R)-amino-2-indanol-based compounds were reported to be selective for the aggrecanases, ADAMTS-4 and -5 over other metalloproteases. To understand the nature of this selectivity for aggrecanases, the inhibitors, along with the broad spectrum metalloprotease inhibitor marimastat, were independently bound to the catalytic domain of ADAMTS-5, and the corresponding crystal structures were determined. By comparing the structures, it was determined that the specificity of the relative inhibitors for ADAMTS-5 was not driven by a specific interaction, such as zinc chelation, hydrogen bonding, or charge interactions, but rather by subtle and indirect factors, such as water bridging, ring rigidity, pocket size, and shape, as well as protein conformation flexibility.
The effect of age on the pharmacokinetics and pharmacodynamics of midazolam (1999)

These results suggest that the lower doses needed to reach sedation in the elderly subjects were attributable to a 50% decrease in EC50, not to changes in pharmacokinetics.
High Speed Shadowgraphy of Transparent Nozzles as an Evaluation Tool for In-Nozzle Cavitation Behavior of GDI Injectors (2017)

Gasoline Direct Injection (GDI) systems have become a rapidly developing technology taking up a considerableand rapidly growing share in the Gasoline Engine market due to the thermodynamic advantages of direct injection. The process of spray formation and propagation from a fuel injector is very crucial in optimizing the air-fuel mixture of DI engines. Previous studies have shown that the presence of some cavitation in high-pressure fuel nozzles can lead to better atomization of the fluid. However, under some very specific circumstances, high levels of cavitation can also delay the atomization process; spray stabilization due to hydraulic flip is the most well-known example. Therefore, a better understanding of cavitation behavior is of vital importance for further optimization of next generation fuel injectors.In contrast to the abundance of investigations conducted on the inner flow and cavitation patterns of diesel injectors, corresponding in-depth research on the inner flow of gasoline direct-injection nozzles is still relatively scarce. In this study, the results of an experiment performed on real-size GDI injector nozzles made of acrylic glass are presented. The inner flow of the nozzle is visualized using a high-power pulsed laser, a long-distance microscope and a high- speed camera. The ambiguity of dark areas on the images, which may represent cavitation regions as well as ambient air drawn into the nozzle holes, is resolved by injecting the fuel both into a fuel or gas filled environment. In addition, the influence of backpressure on the transient flow characteristics of the internal flow is investigated. In good agreement with observations made in previous studies, higher backpressure levels decrease the amount of cavitation inside the nozzles. Due to the high temporal and spatial resolution of the experiment, the transient cavitation behavior during the opening, quasi-steady and closing phases of the injector needle motion can be analyzed. For example, it is found that cavitation patterns oscillate with a characteristic frequency that depends on the backpressure. The link between cavitation and air drawn into the nozzle at the beginning of injection is alsorevealed.DOI: http://dx.doi.org/10.4995/ILASS2017.2017.4639
Identification of novel RHPS4-derivative ligands with improved toxicological profiles and telomere-targeting activities (2014)

The pentacyclic acridinium salt RHPS4 (3,11-difluoro-6,8,13-trimethyl-8H-quino [4,3,2-kl] acridinium methosulfate, compound 1) is one of the most interesting DNA G-quadruplex binding molecules due to its high efficacy in tumor cell growth inhibition both in in vitro models and in vivo against human tumor xenografts in combination with conventional chemotherapeutics. Despite compound 1 having desirable chemical and pharmaceutical properties, its potential as a therapeutic agent is compromised by off-target effects on cardiovascular physiology. In this paper we report a new series of structurally-related compounds which were developed in an attempt to minimize its off-target profile, but maintaining the same favorable chemical and pharmacological features of the lead compound. By performing a comparative analysis it was possible to identify which derivatives had the following properties: (i) to show a reduced capacity in respect to compound 1 to inhibit the hERG tail current tested in a patch clamp assay and/or to interact with the human recombinant β2 receptor; (ii) to maintain both a good G4-binding affinity and cancer cell selectivity; and (iii) to trigger DNA damage with specific telomere uncapping. These studies allowed us to identify a novel G4-stabilizing molecule, compound 8, being characterized by reduced off-target effects and potent telomere on-target properties compared to the prototypic compound 1. Moreover, compound 8 shares with compound 1 the same molecular mode of action and an anti-tumour activity specifically restricted to replicating cells, as evident with its particularly efficient activity in combination therapy with a topoisomerase I inhibitor. In conclusion, we have identified a new pentacyclic derivative 8 having suitable properties to be the focus of further investigations as a clinical candidate for cancer therapy.
Piecewise Mixed Effects Model to Compare the Weight-gain Patter ns Before and After Diagnosis of Asthma in Children Younger than 5 Years (2015)

Asthma and obesity are two significant public health problems that both originate in early childhood and have shared risk factors and manifestations. Studies suggest a strong association between asthma development and subsequent accelerated weight gain. Children are diagnosed with asthma in early childhood and are often exposed to factors associated with rapid weight gain. This article intends to demonstrate an innovative application of the piecewise mixed effects model to characterize the difference in the temporal rate of change in BMIz, the standardized scores of body mass index and weight-for-length that measure weight status, before and after asthma diagnosis in children younger than 5 years. The data consist of unique sequences from 1194 children's clinic visits during the first 5 years of life. We used a knot at the time of diagnosis and detected a differential weight-gain pattern before and after asthma diagnosis. The pre-and post-asthma-diagnosis weight-gain patterns further differ by sex and race-ethnicity. After asthma diagnosis, female children showed a higher increase in the rate of change in BMIz than males. Non-Hispanic African Americans and Hispanics had higher post-diagnosis rates of change in BMIz than Caucasians. The differential weight-gain patterns between male and female children were mainly contributed by Caucasian children. These findings could have important implications in the clinical care of children after asthma diagnosis.
Hardware-Efficient Duobinary Neural Network Equalizers for 800 Gb/s IM/DD PAM4 Transmission Over 10 km SSMF (2023)

In this article, we discuss challenges and options for scaling IM/DD transceivers towards 800 Gbps. Our focus is CWDM4 PAM4 transmission and our target distance is 10 km in O-band, which is a most urgent use case for next generation optical short reach systems like data centre interconnects and networks. At this reach and rate, chromatic dispersion (CD) becomes the main challenge. Its mitigation is essential and primarily done with digital signal processing. State of the art techniques, however, make transceivers quickly too complex. We show upon measurement results how neural network equalization can meet Volterra equalization performance with 30% less hardware multiplier complexity. When also applying magnitude weight pruning, an additional 43% reduction is possible without performance loss across all CWDM4 lanes. If needed, an added MLSE stage can further push performance in both cases. In any of these configurations, a key enabler against strong CD penalties is duobinary training, which is applicable to all feed-forward equalization architectures.
A Turnstile Mechanism for the Controlled Growth of Biosynthetic Intermediates on Assembly Line Polyketide Synthases (2016)

Vectorial polyketide biosynthesis on an assembly line polyketide synthase is the most distinctive property of this family of biological machines, while providing the key conceptual tool for the bioinformatic decoding of new antibiotic pathways. We now show that the action of the entire assembly line is synchronized by a previously unrecognized turnstile mechanism that prevents the ketosynthase domain of each module from being acylated by a new polyketide chain until the product of the prior catalytic cycle has been passed to the downstream module from the corresponding acyl carrier protein domain. The turnstile is closed by virtue of tight coupling to the signature decarboxylative condensation reaction catalyzed by the ketosynthase domain of each polyketide synthase module. Reopening of the turnstile is coupled to the eventual chain translocation step that vacates the module. At the maximal rate of substrate turnover, one would expect the chain release step to initiate a cascade of chain translocation events that sequentially migrate back upstream, thereby repriming each module and setting up the assembly line for the next round of polyketide chain elongation.
Correlation between Surface Structure and Charge Ordering in Magnetite(001) Studied by Scanning Tunneling Microscopy and Spectroscopy (2007)

We report the observation on the charge ordering of Fe ions in a magnetite(Fe3O4)(001) film surface by scanning tunneling microscopy and spectroscopy (STM/STS) with a nonmagnetic W tip. The Fe3O4(001) film surface exhibits a B-plane termination with a (√2 × √2)R45° reconstruction. Fe cation rows running along the [110] direction show a wavelike structure. The (√2 × √2)R45° surface reconstruction is originated from the wavelike Fe rows. The current imaging tunneling spectroscopy image shows alternation of two different kinds of current peak with a separation of about 0.6 nm. Each current peak arises from the same local density of states (LDOS) of two Fe ions. The presence of Fe dimers with two different kinds of LDOS provides evidence for the charge ordering of Fe ions with different charge states. STM and STS using a nonmagnetic W tip allow us to correlate the charge ordering pattern with the surface structure.
Use of constraints in the superresolution of passive millimeter-wave images (2003)

This paper discusses the use of constraints when super-resolving passive millimeter wave (PMMW) images. A PMMW imager has good all-weather imaging capability but requires a large collection aperture to obtain adequate spatial resolution due to the diffraction limit and the long wavelengths involved. A typical aperture size for a system operating at 94GHz would be 1m in diameter. This size may be reduced if image restoration techniques are employed. A factor of two in recognition range may be achieved using a linear technique such as a Wiener filter; while a factor of four is available using non-linear techniques. These non-linear restoration methods generate the missing high frequency information above the pass band in band limited images. For this bandwidth extension to generate genuine high frequencies, it is necessary to restore the image subject to constraints. These constraints should be applied directly to the scene content rather than to any noise that might also be present. The merits of the available super-resolution techniques are discussed with particular reference to the Lorentzian method. Attempts are made to explain why the distribution of gradients within an image is Lorentzian by assuming that an image has randomly distributed gradients of random size. Any increase in sharpness of an image frequently results in an increase in the noise present. The effect of noise and image sharpness on the ability of a human observer to recognise an object in the scene is discussed with reference to a recent model of human perception.
Case Study: Pipe Network Model Calibration Issues (1986)

This paper illustrates that it is possible to calibrate accurately a mathematical model of a complicated water distribution system (271 nodes, 307 pipes, 9 pressure reducing valves) if adequate and accurate data are collected. It is essential that the model be calibrated for a range of water use rates and patterns as otherwise it is possible for the model to appear to be calibrated even though it contains significant errors. For example, in this system it was possible to make the model appear calibrated for C‐factors that varied by a factor of 3 provided that sufficient errors were made on other input parameters. The key to collecting adequate data is that the head at boundary nodes (pumps, tanks, pressure reducing valves) be known when pressure readings are made in the system.
Structure of Organic/Inorganic Interface in Assembled Materials Comprising Molecular Components. Crystal Structure of the Sensitizer Bis[(4,4‘-carboxy-2,2‘-bipyridine)(thiocyanato)]ruthenium(II) (1998)

Structural data have been obtained for the photosensitizer bis[(4,4‘-carboxy-2,2‘-bipyridine)(thiocyanato)]ruthenium(II) (1) via X-ray diffraction analysis. Crystals of 1 are triclinic, a = 11.4663(4) Å, b = 12.5897(5) Å, c = 18.9329(7) Å, α = 75.238(2)°, β = 89.611(2)°, γ = 66.446(2)°, space group P1̄, Z = 2, refinement to R = 0.0809, Rw = 0.0950 for 4045 observed reflections. Structural models of sensitizer molecules anchoring to the TiO2 anatase surface and models of close-packed sensitizer monolayers with different anchoring types have been built by using experimental geometry of known organic Ti complexes and the X-ray structure of sensitizer 1. On the basis of a simple one-dimensional tight-binding model, it was suggested that possible modifications of TiO2/sensitizer interface could enhance interfacial transparency for injected electrons.
Preparation of Shell Cross‐Linked Micelles by Polyelectrolyte Complexation (2004)

Mit Schale genießen: Micellen mit vernetzten Schalen (SCL-Micellen; 3) wurden durch Polyelektrolyt-Komplexierung eines micellenbildenden kationischen ABC-Triblockcopolymers (1) mit einem anionischen Diblockcopolymer-Linker (2) hergestellt. Die polymeren Reagentien lagern sich in wässriger Lösung bei Raumtemperatur schnell zusammen. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2004/z52428_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Parametric macromodeling based on amplitude and frequency scaled systems with guaranteed passivity (2011)

SUMMARY We propose a novel parametric macromodeling method for systems described by scattering parameters, which depend on multiple design variables such as geometrical layout or substrate features. It is able to build accurate multivariate macromodels that are stable and passive over the entire design space. Poles and residues are parameterized indirectly. The proposed method is based on an efficient and reliable combination of rational identification, a procedure to find amplitude and frequency scaling system coefficients and positive interpolation schemes. Pertinent numerical examples validate the proposed parametric macromodeling technique. Copyright © 2011 John Wiley &amp; Sons, Ltd.
ChemInform Abstract: Synthesis and Pharmacologic Evaluation of 2‐endo‐Amino‐3‐exo‐ isopropylbicyclo(2.2.1)heptane: A Potent Imidazoline1 Receptor Specific Agent. (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
SALAD: Self-Adaptive Lightweight Anomaly Detection for Real-time\n Recurrent Time Series (2021)

Real-world time series data often present recurrent or repetitive patterns\nand it is often generated in real time, such as transportation passenger\nvolume, network traffic, system resource consumption, energy usage, and human\ngait. Detecting anomalous events based on machine learning approaches in such\ntime series data has been an active research topic in many different areas.\nHowever, most machine learning approaches require labeled datasets, offline\ntraining, and may suffer from high computation complexity, consequently\nhindering their applicability. Providing a lightweight self-adaptive approach\nthat does not need offline training in advance and meanwhile is able to detect\nanomalies in real time could be highly beneficial. Such an approach could be\nimmediately applied and deployed on any commodity machine to provide timely\nanomaly alerts. To facilitate such an approach, this paper introduces SALAD,\nwhich is a Self-Adaptive Lightweight Anomaly Detection approach based on a\nspecial type of recurrent neural networks called Long Short-Term Memory (LSTM).\nInstead of using offline training, SALAD converts a target time series into a\nseries of average absolute relative error (AARE) values on the fly and predicts\nan AARE value for every upcoming data point based on short-term historical AARE\nvalues. If the difference between a calculated AARE value and its corresponding\nforecast AARE value is higher than a self-adaptive detection threshold, the\ncorresponding data point is considered anomalous. Otherwise, the data point is\nconsidered normal. Experiments based on two real-world open-source time series\ndatasets demonstrate that SALAD outperforms five other state-of-the-art anomaly\ndetection approaches in terms of detection accuracy. In addition, the results\nalso show that SALAD is lightweight and can be deployed on a commodity machine.\n
Polysaccharide Based Nanoparticles (2018)

Abstract Nanoparticles made of biodegradable polymers have outstanding merits as a drug delivery system. Polysaccharide‐based nanoparticles have been well explored because of their safety, stability, biocompatibility, biodegradability and hydrophilicity. The present review emphasizes the efforts articulated to improve polysaccharide‐based nanoparticles as drug delivery tool for effective therapy and site‐specific targeting of mainly anticancer agents. This review updates reports of recent research on polysaccharides‐based systems particularly chitosan, alginate, cyclodextrins, hyaluronic acid, pullulan, dextran and their combinations with potential applications.
Enhancement of Adaptive Immunity to Neisseria gonorrhoeae by Local Intravaginal Administration of Microencapsulated Interleukin 12 (2013)

Gonorrhea remains one of the most frequent infectious diseases, and Neisseria gonorrhoeae is emerging as resistant to most available antibiotics, yet it does not induce a state of specific protective immunity against reinfection. Our recent studies have demonstrated that N. gonorrhoeae proactively suppresses host T-helper (Th) 1/Th2-mediated adaptive immune responses, which can be manipulated to generate protective immunity. Here we show that intravaginally administered interleukin 12 (IL-12) encapsulated in sustained-release polymer microspheres significantly enhanced both Th1 and humoral immune responses in a mouse model of genital gonococcal infection. Treatment of mice with IL-12 microspheres during gonococcal challenge led to faster clearance of infection and induced resistance to reinfection, with the generation of gonococcus-specific circulating immunoglobulin G and vaginal immunoglobulin A and G antibodies. These results suggest that local administration of microencapsulated IL-12 can serve as a novel therapeutic and prophylactic strategy against gonorrhea, with implications for the development of an effective vaccine.
Relationships between Poly(ethylene glycol) Modifications on RNA–Spherical Nucleic Acid Conjugates and Cellular Uptake and Circulation Time (2016)

Two synthetic approaches that allow one to control PEG content within spherical nucleic acids (SNAs) have been developed. One approach begins with RNA-modified gold nanoparticles followed by a backfill of PEG 2K alkanethiols, and the other involves co-adsorption of the two entities on a gold nanoparticle template. These two methods have been used to explore the role of PEG density on the chemical and biological properties of RNA-SNAs. Such studies show that while increasing the extent of PEGylation within RNA-SNAs extends their blood circulation half-life in mice, it also results in decreased cellular uptake. Modified ELISA assays show that constructs, depending upon RNA and PEG content, have markedly different affinities for class A scavenger receptors, the entities responsible, in part, for cellular internalization of SNAs. In designing SNAs for therapeutic purposes, these competing factors must be considered and appropriately adjusted depending upon the desired use.
Cellular Mechanisms Of Thermal Injury In Electrical Trauma (2005)

In this study we investigate the cellular mechanisms of thermal damage to skeletal muscle cells to quantify the role of thermal injury in electrical trauma. The effects of elevated temperature on the plasma membrane and contraction behavior of cells were investigated by microscopic methods. The results suggest that thermal injury may lead to cellular injury by excessive contraction andlor denaturation of membrane proteins at temperatures greater than 45OC.