gebhart/patrepeval huggingface dataset:
Chemical Probes that Competitively and Selectively Inhibit Stat3 Activation (2009)

Signal transducer and activator of transcription (Stat) 3 is an oncogene constitutively activated in many cancer systems where it contributes to carcinogenesis. To develop chemical probes that selectively target Stat3, we virtually screened 920,000 small drug-like compounds by docking each into the peptide-binding pocket of the Stat3 SH2 domain, which consists of three sites--the pY-residue binding site, the +3 residue-binding site and a hydrophobic binding site, which served as a selectivity filter. Three compounds satisfied criteria of interaction analysis, competitively inhibited recombinant Stat3 binding to its immobilized pY-peptide ligand and inhibited IL-6-mediated tyrosine phosphorylation of Stat3. These compounds were used in a similarity screen of 2.47 million compounds, which identified 3 more compounds with similar activities. Examination of the 6 active compounds for the ability to inhibit IFN-gamma-mediated Stat1 phosphorylation revealed that 5 of 6 were selective for Stat3. Molecular modeling of the SH2 domains of Stat3 and Stat1 bound to compound revealed that compound interaction with the hydrophobic binding site was the basis for selectivity. All 5 selective compounds inhibited nuclear-to-cytoplasmic translocation of Stat3, while 3 of 5 compounds induced apoptosis preferentially of breast cancer cell lines with constitutive Stat3 activation. Thus, virtual ligand screening of compound libraries that targeted the Stat3 pY-peptide binding pocket identified for the first time 3 lead compounds that competitively inhibited Stat3 binding to its pY-peptide ligand; these compounds were selective for Stat3 vs. Stat1 and induced apoptosis preferentially of breast cancer cells lines with constitutively activated Stat3.
Human mitogen-activated protein kinase kinase 4 as a candidate tumor suppressor. (1997)

Mitogen-activated protein kinases function in signal transduction pathways that are involved in controlling key cellular processes in many organisms. A mammalian member of this kinase family, MKK4/JNKK1/SEK1, has been reported to link upstream MEKK1 to downstream stress-activated protein kinase/JNK1 and p38 mitogen-activated protein kinase. This mitogen-activated protein kinase pathway has been implicated in the signal transduction of cytokine- and stress-induced apoptosis in a variety of cell types. Here, we report that two human tumor cell lines, derived from pancreatic carcinoma and lung carcinoma, harbor homozygous deletions that eliminate coding portions of the MKK4 locus at 17p, located approximately 10 cM centromeric of p53. In addition, in a set of 88 human cancer cell lines prescreened for loss of heterozygosity, we detected two nonsense and three missense sequence variants of MKK4 in cancer cell lines derived from human pancreatic, breast, colon, and testis cells. In vitro biochemical assays revealed that, when stimulated by MEKK1, four of the five altered MKK4 proteins lacked the ability to phosphorylate stress-activated protein kinase. Thus, the incidence of coding mutations of MKK4 in the set of cell lines is 6 of 213 (approximately 3%). These findings suggest that MKK4 may function as a suppressor of tumorigenesis or metastasis in certain types of cells.
Intermolecular recombination between DNAs introduced into mouse L cells is mediated by a nonconservative pathway that leads to crossover products. (1990)

We describe experiments designed to measure the efficiency of intermolecular recombination between mutant herpesvirus thymidine kinase (tk) genes introduced into mouse L cells. Recombinants were scored as stable transformants containing a functional tk gene. The two recombination substrates used were ptkB8, a pBR322-based plasmid containing a mutant tk gene, with a BamHI linker in an SphI restriction site that is centrally located within the gene, and mp10tk delta 3' delta 5', an mp10 vector with a tk gene deleted at both the 3' and 5' ends. The only homology shared by the two DNAs is 885 base pairs within the tk gene. To determine whether the double-strand break repair model that has been used to explain recombination in yeast cells (J. W. Szostak, T. L. Orr-Weaver, R. J. Rothstein, and F. W. Stahl, Cell 33:25-35, 1983) can account for recombination during the introduction of these DNAs into mammalian cells, we transformed cells with BamHI-linearized ptkB8 and supercoiled mp10tk delta 3' delta 5' replicative-form DNA. These two DNAs should recombine efficiently according to that model and should generate gene conversion products. In this reaction, the supercoiled DNA acts as the donor of information to repair the cleaved tk gene. Our results indicated that the efficiency of this reaction was very low (less than 10 transformants were obtained per 0.1 microgram of each DNA used in the reaction per 10(6) cells). In contrast, if BamHI-cleaved ptkB8 DNA was cotransformed into cells along with a circular DNA molecule containing a tk gene deleted only at its 3' end or only at its 5' end (mp10tk delta 3' or mp10tk delta 5'), then the efficiency of recombination could be more than 4 orders of magnitude higher than it was with circular mp10tk delta 3' delta 5' DNA. Recombination frequencies were highest when the tk delta 3' or tk delta 5' DNA used was cleaved at the tk deletion junction. Southern analyses of DNA from TK+ transformants generated with BamHI-cleaved ptkB8 and BamHI-cleaved mp10tk delta 3' DNAs indicated that recombination was almost always associated with the reassortment of markers flanking the reconstructed tk DNA. Together, these results are more consistent with the nonconservative single-strand annealing model for recombination that we proposed several years ago (F.-L. Lin, K. Sperle, and N. Sternberg, Mol. Cell. Biol. 4:1020-1034, 1984) than they are with the double-strand break repair model.
Past, Present, and Pending Intellectual Property for Electromagnetic Heating of Oil Shale (2008)

The reason patents, otherwise referred to as prior art, are an excellent source of information is the requirement that the patent application discloses how to build and/or operate an invention. While many patent attorneys and inventors feel they are being clever by keeping their disclosure nebulous as possible with the hopes of making their claims broader, my opinion of the patents we will be reviewing is their inventors and attorney’s did an excellent job of describing their inventions – thus making them an excellent resource for the researcher.
Electrostatic and small-signal analysis of CMUTs with circular and square anisotropic plates (2015)

Traditionally, capacitive micromachined ultrasonic transducers (CMUTs) are modeled using the isotropic plate equation, and this leads to deviations between analytical calculations and finite element modeling (FEM). In this paper, the deflection is calculated for both circular and square plates using the full anisotropic plate equation. It is shown that the anisotropic calculations match excellently with FEM, whereas an isotropic approach causes up to 10% deviations in deflection. For circular plates, an exact solution can be found. For square plates using the Galerkin method, and utilizing the symmetry of the silicon crystal, a compact and accurate expression for the deflection can be obtained. The deviation from FEM in center deflection is <0.1%. The theory of multilayer plates is also applied to the CMUT. The deflection of a square plate was measured on fabricated CMUTs using a white light interferometer. Fitting the plate parameter for the anisotropic calculated deflection to the measurement, a deviation of 0.07% is seen. Electrostatic and small-signal dynamic analysis are performed using energy considerations including anisotropy. The stable position, effective spring constant, pullin distance, and pull-in voltage are found for both circular and square anisotropic plates, and the pressure dependence is included by comparison with the corresponding analysis for a parallel plate. Measurements on fabricated devices with both circular and square plates subjected to increasing bias voltage are performed, and it is observed that the models including anisotropic effects are within the uncertainty interval of the measurements. Finally, a lumped element small-signal model for both circular and square anisotropic plates is derived to describe the dynamics of the CMUT.
Enhancement of Morphological Plasticity in Hippocampal Neurons by a Physically Modified Saline via Phosphatidylinositol-3 Kinase (2014)

Increase of the density of dendritic spines and enhancement of synaptic transmission through ionotropic glutamate receptors are important events, leading to synaptic plasticity and eventually hippocampus-dependent spatial learning and memory formation. Here we have undertaken an innovative approach to upregulate hippocampal plasticity. RNS60 is a 0.9% saline solution containing charge-stabilized nanobubbles that are generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP) flow under elevated oxygen pressure. RNS60, but not NS (normal saline), PNS60 (saline containing a comparable level of oxygen without the TCP modification), or RNS10.3 (TCP-modified normal saline without excess oxygen), stimulated morphological plasticity and synaptic transmission via NMDA- and AMPA-sensitive calcium influx in cultured mouse hippocampal neurons. Using mRNA-based targeted gene array, real-time PCR, immunoblot, and immunofluorescence analyses, we further demonstrate that RNS60 stimulated the expression of many plasticity-associated genes in cultured hippocampal neurons. Activation of type IA, but not type IB, phosphatidylinositol-3 (PI-3) kinase by RNS60 together with abrogation of RNS60-mediated upregulation of plasticity-related proteins (NR2A and GluR1) and increase in spine density, neuronal size, and calcium influx by LY294002, a specific inhibitor of PI-3 kinase, suggest that RNS60 upregulates hippocampal plasticity via activation of PI-3 kinase. Finally, in the 5XFAD transgenic model of Alzheimer's disease (AD), RNS60 treatment upregulated expression of plasticity-related proteins PSD95 and NR2A and increased AMPA- and NMDA-dependent hippocampal calcium influx. These results describe a novel property of RNS60 in stimulating hippocampal plasticity, which may help AD and other dementias.
Highly Efficient and Versatile Anodes for Biofuel Cells Based on Cellobiose Dehydrogenase from <i>Myriococcum thermophilum</i> (2008)

A powerful alternative to glucose oxidase as anode material in implantable biofuel cells is presented: Cellobiose dehydrogenase (CDH) from the ascomycete Myriococcum thermophilum (MtCDH) catalyzes the electrochemical oxidation of glucose, lactose, and cellobiose over a broad pH range. Current densities of more than 1 mA·cm−2 can be reached when MtCDH is wired to an Os redox polymer in the presence of single-walled carbon nanotubes and when lactose is used as a substrate at pH 8. In contrast to CDHs from basidiomycete fungi, which oxidize only β-1,4-linked di- and oligosaccharides efficiently, MtCDH is also able to oxidize glucose and other monosaccharides at relatively high turnover rates. The current density toward oxidation of 5 mM glucose under physiological conditions was about 100 μA·cm−2. Outstanding properties of MtCDH are high-temperature stability; a strong discrimination of oxygen turnover (and therefore no H2O2 production) in the presence of alternative electron acceptors; an ability to oxidize a range of carbohydrates, and a working pH from 3 to 10, which allows for combination with a variety of enzyme-based cathodes for oxygen reduction. The performance and stability of a membraneless glucose biofuel cell consisting of an MtCDH-modified anode and a Pt black cathode working under physiological conditions (PBS buffer, pH 7.4, 37 °C) were investigated over a period of 3 days. A maximum voltage of 500 mV, a maximum current density of almost 700 μA·cm−2, and a maximum power density of 157 μW·cm−2 at an operating voltage of 280 mV (under oxygen purging/nonquiescent conditions) could be obtained with glucose (100 mM) as the substrate. Furthermore, the direct and mediated electron-transfer properties of MtCDH are compared in this work. The electrocatalytic current detected for mediated electron transfer (MET) is much higher and starts at a less positive potential than that for direct electron transfer (DET). The reason is that, in MET, the Os redox polymer is able to collect the electrons from the catalytically active flavin domain, whereas DET requires the oxidation of the heme domain, which has a more positive redox potential. The electrocatalytic current densities for DET and MET are significantly increased in the presence of single-walled carbon nanotubes.
Plasma sources for electrons and ion beams (1999)

Plasma devices are commonly used for the production of ion beams. It has been demonstrated that the multicusp generator can produce very low energy ion beams for ion projection lithography applications. The multicusp source has also found important applications in focused ion beam systems. With its high and uniform plasma density, attempts have been made to extract high brightness electron beams from this type of plasma source, making it also useful for electron beam lithography applications.
Who succeeds in jail diversion programs for persons with mental illness? A multi‐site study (2009)

This study examined how the characteristics of people with mental illness who are participants in post-booking jail diversion programs affect recidivism and time spent incarcerated. The study employed data from a multi-site, federally funded jail diversion initiative. A pre-post comparison design was used to compare experiences of arrest and days spent in jail of diverted individuals for the 12 months following enrollment with the 12 months prior to enrollment. Also compared were differences in 12-month public safety outcomes. Data were collected between February 2003 and August 2007. The findings suggest that people with mental illness who are diverted from jail to community-based services experience fewer arrests and jail days. Approximately half of the sample were never arrested during the 12 months following enrollment. The strongest differences between people who experienced reduced contact with the criminal justice system and people with unchanged or increased contact were found in measures of criminal history. The results suggest that services targeted to diverted individuals with mental illness should address public safety goals, not just those of public health.
Regulation of interleukin-1 and tumour necrosis factor gene expression in myelomonocytic cell lines by 1,25-dihydroxyvitamin D3. (1991)

1,25-dihydroxyvitamin D3[1,25-(OH)2D3] is capable of regulating cells in the immune system and affects cytokine production by both T lymphocytes and by monocytes. We examined the effects of 1,25-(OH)2D3 on the regulation of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) genes in HL-60 and U937 cells. 1,25-(OH)2D3 alone only induced low level expression of the genes for these cytokines. Phorbol 12-myristate 13-acetate (PMA) strongly induced the transcription of these genes, whilst the addition of 1,25-(OH)2D3 to PMA-stimulated cells caused a further dose-dependent synergistic increase in the mRNA for both cytokines in U937 cells. In PMA-stimulated HL-60 cells, 1,25-(OH)2D3 increased the mRNA for IL-1 beta but not that for TNA-alpha, These differences may be related to the different stage of myeloid differentiation in HL-60 and U937 cells.
Villification: How the Gut Gets Its Villi (2013)

The villi of the human and chick gut are formed in similar stepwise progressions, wherein the mesenchyme and attached epithelium first fold into longitudinal ridges, then a zigzag pattern, and lastly individual villi. We find that these steps of villification depend on the sequential differentiation of the distinct smooth muscle layers of the gut, which restrict the expansion of the growing endoderm and mesenchyme, generating compressive stresses that lead to their buckling and folding. A quantitative computational model, incorporating measured properties of the developing gut, recapitulates the morphological patterns seen during villification in a variety of species. These results provide a mechanistic understanding of the formation of these elaborations of the lining of the gut, essential for providing sufficient surface area for nutrient absorption.
Limits of cardiac compensation in anemic baboons. (1988)

The risk of homologous blood may cause physicians to withhold red cell treatment after acute blood loss. We believe that in the euvolemic patient with acute anemia, the heart is the principal organ at risk. The cardiac compensation to extreme anemia is unknown and is the purpose of this report. Fourteen adult baboons were anesthetized, paralyzed, and ventilated with room air. Left atrial and coronary sinus catheters were inserted surgically. Experimental animals (n = 7) were hemodiluted at constant left atrial pressure with 5% human serum albumin. Control animals (n = 7) underwent similar volume exchanges with fresh, cross-matched, homologous red blood cells resuspended in human serum albumin, also at constant left atrial pressure. Six of seven experimental animals survived until hematocrit levels were 4%. Adequate cardiac compensation was observed until hematocrit levels were less than 10%. Increased flow, without increases in the O2 extraction ratio, was the mechanism of compensation used by the healthy heart with patent coronary vessels.
Standard cell library optimization for leakage reduction (2006)

Scaling device geometries have caused leakage-power consumption to be one of the major challenges of deep sub-micron design and a major source for parametric yield loss. We propose a library optimization approach involving generation of additional variants for each cell master, by biasing gate-lengths of devices. We employ transistor-level gate-length assignment to exploit asymmetries in standard cell circuit topology as well slack distribution of the design. The enhanced library is used by a power optimizer to reduce design leakage without violating any timing constraints. Such transistor-level optimization of cell libraries offers significantly better leakage-delay tradeoff than simple cell-level biasing (CLB) proposed previously. Experimental results on benchmarks show transistor-level biasing (TLB) can improve the CLB leakage optimization results by 8-17%. There is a corresponding improvement in design leakage distribution as well.
IIP2 and DC Offsets in the Presence of Leakage at LO Frequency (2006)

Device mismatch in a mixer is generally believed to be the major contributor of second-order distortion that limits the performance of a direct conversion receiver. In this brief, we show that even with perfect matching, leakage at local oscillator frequency prior to mixing creates large second-order distortion when the third-order input intercept point of the receiver is not sufficiently large. Measurement data from a quad-band global system for mobile communications/global packet radio service transceiver implemented in 90-nm digital CMOS process is also presented to support our claim
Improving resolution of miniature spectrometers by exploiting sparse nature of signals (2012)

In this paper, we present a signal processing approach to improve the resolution of a spectrometer with a fixed number of low-cost, non-ideal filters. We aim to show that the resolution can be improved beyond the limit set by the number of filters by exploiting the sparse nature of a signal spectrum. We consider an underdetermined system of linear equations as a model for signal spectrum estimation. We design a non-negative L1 norm minimization algorithm for solving the system of equations. We demonstrate that the resolution can be improved multiple times by using the proposed algorithm.
A Review on the Analysis of Building with Different Types of Bracings (2022)

Abstract: Bracing is one of the most extensively used lateral load resisting systems in multi-storied frame structure. It helps in reducing structure damage or collapse during an earthquake. To know the responses of providing bracings in high rise buildings is the aim of this study. Hence, it is necessary to demonstrate work on the analysis, design and post effects of bracings when seismic forces act in a building. In this paper, a review is taken out over the analysis and design of buildings with and without bracings to study more detail analytical results and conclusions to find its effectiveness in reducing the impact of lateral loads on high rise buildings in case of an earthquake. Keywords: earthquake, bracings, ETABS, SAP2000, StaadPro
Electroactive Shape‐Memory Polyurethane Composites Incorporating Carbon Nanotubes (2005)

Abstract Summary: Electro‐active shape‐memory composites were synthesized using conducting polyurethane (PU) composites and multi‐walled carbon nanotubes (MWNTs). Surface modification of the MWNTs (by acid treatment) improved the mechanical properties of the composites. The modulus and stress at 100% elongation increased with increasing surface‐modified MWNT content, while elongation at break decreased. MWNT surface modification also resulted in a decrease in the electrical conductivity of the composites, however, as the surface modified MWNT content increased the conductivity increased (an order of 10 −3 S · cm −1 was obtained in samples with 5 wt.‐% modified‐MWNT content). Electro‐active shape recovery was observed for the surface‐modified MWNT composites with an energy conversion efficiency of 10.4%. Hence, PU‐MWNT composites may prove promising candidates for use as smart actuators. The electro‐active shape‐recovery behavior of PU‐MWNT composites. The pictured transition occurs within 10 s when a constant voltage of 40 V is applied. magnified image The electro‐active shape‐recovery behavior of PU‐MWNT composites. The pictured transition occurs within 10 s when a constant voltage of 40 V is applied.
Evidence for paralytic shellfish poisons in the freshwater cyanobacterium Lyngbya wollei (Farlow ex Gomont) comb. nov (1997)

Lyngbya wollei (Farlow ex Gomont) comb. nov., a perennial mat-forming filamentous cyanobacterium prevalent in lakes and reservoirs of the southeastern United States, was found to produce a potent, acutely lethal neurotoxin when tested in the mouse bioassay. Signs of poisoning were similar to those of paralytic shellfish poisoning. As part of the Tennessee Valley Authority master plan for Guntersville Reservoir, the mat-forming filamentous cyanobacterium L. wollei, a species that had recently invaded from other areas of the southern United States, was studied to determine if it could produce any of the known cyanotoxins. Of the 91 field samples collected at 10 locations at Guntersville Reservoir, Ala., on the Tennessee River, over a 3-year period, 72.5% were toxic. The minimum 100% lethal doses of the toxic samples ranged from 150 to 1,500 mg kg of lyophilized L. wollei cells-1, with the majority of samples being toxic at 500 mg kg-1. Samples bioassayed for paralytic shellfish toxins by the Association of Official Analytical Chemists method exhibited saxitoxin equivalents ranging from 0 to 58 micrograms g (dry weight)-1. Characteristics of the neurotoxic compound(s), such as the lack of adsorption by C18 solid-phase extraction columns, the short retention times on C18 high-performance liquid chromatography (HPLC) columns, the interaction of the neurotoxins with saxiphilin (a soluble saxitoxin-binding protein), and external blockage of voltage-sensitive sodium channels, led to our discovery that this neurotoxin(s) is related to the saxitoxins, the compounds responsible for paralytic shellfish poisonings. The major saxitoxin compounds thus far identified by comparison of HPLC fluorescence retention times are decarbamoyl gonyautoxins 2 and 3. There was no evidence of paralytic shellfish poison C toxins being produced by L. wollei. Fifty field samples were placed in unialgal culture and grown under defined culture conditions. Toxicity and signs of poisoning for these laboratory-grown strains of L. wollei were similar to those of the field collection samples.