gebhart/patrepeval huggingface dataset:
Combination of HDACi entinostat (SNDX-275) with letrozole provides control over tumor growth in MDA-MB-231 xenograft model. (2009)

Abstract Abstract #6128 It is well established that approximately 75% of human breast cancers are ER+ and therefore treated with endocrine therapy. In a past few decades endocrine therapy has made significant advancements. However, the application of these agents is limited to ER+ cancers since ER- patients are unresponsive to endocrine therapy primarily due to lack of ER expression in the tumor. The main purpose of this project is to determine whether ER- breast cancer tumors that display poor anti-proliferative response to aromatase inhibitor (AI) letrozole, can be sensitized by co-treatment with HDACi entinostat. Based on preliminary studies, we hypothesize that by inhibiting HDAC ER is re-expressed making the cells sensitive to the anti-proliferative effects of AIs. In our previous studies we have shown that HDACi entinostat can revert the ERα repression and upregulate ERα and aromatase in vitro and in vivo. In this study we are showing that this activation of aromatase and re-expression of ERα renders ER- breast cancer tumors (xenografts of MDA-MB-231 cells) responsive to letrozole.&#x2028; MDA-MB-231 xenografts were grown in ovariectomized female nude mice. Mice were inoculated with 2.5X 106 cells per site subcutaneously. When the tumors reached a measurable size ∼150 mm3, the mice were grouped into 6 groups (n=10), such that the mean tumor volumes across the groups was not statistically different (p=0.99). The mice were injected with Δ4A (100 μg/day), Δ4A plus letrozole (10 μg/day), entinostat (2.5 mg/kg/day), entinostat plus Δ4A, entinostat plus Δ4A plus letrozole or vehicle. The mice were injected 5 times a week. The tumors were measured every week with calipers and the tumor volumes were calculated using formula, 4/3 π r12r2. The mice in the entinostat plus Δ4A plus letrozole group had the least tumor growth rate (0.004+0.081), which was lower than entinostat plus Δ4A (0.115+0.079) and Δ4A plus letrozole (0.096+0.080). This data suggests a trend towards improved inhibition of tumor growth with combination of entinostat plus letrozole. The mice were sacrificed on week 9 due to large tumor volumes. The tumors and uteri were excised, cleaned, weighed and stored for additional analysis.&#x2028; In addition, ability of this combination to inhibit migration in vitro was examined by wound healing assay. The combination of entinostat plus letrozole provides superior inhibition of migration (p&lt;0.001) compared to control, entinostat and letrozole alone. This suggests that the combination of entinostat plus letrozole has potential of inhibiting metastatic spread along with tumor growth.&#x2028; These findings indicate that ERα in ER- breast cancer cells is silenced along with aromatase but can be restored with HDACi. Thus activation of silenced ER and intratumoral aromatase by HDACi could open a new avenue for management of ER- advanced breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6128.
Gain spiking and mode-beating control by signal injection in CO2 lasers (1977)

Gain spiking and mode-beating effects in a high-power pulsed CO2 laser have been experimentally shown to be controllable by the injection of a low-power signal. The laser was pumped by a 1-atm 10–100- kW/cm3 discharge controlled by a 175-kV e-beam at 0.4 A/cm2. A line-selectable low-power CO2 laser beam was injected on axis into the relatively large Fresnel number square unstable resonator cavity of the pulsed laser through a centered hole in the primary mirror. Analysis of the pulse output without signal injection showed as many as eight longitudinal modes were present which produced beats. On rare occasions the beat pattern envelope was seen to rise above the gain spike. Injecting a cw plane-polarized 0.3-W P-20 signal into the CO2 oscillator cavity caused the pulsed laser to operate plane polarized at a single frequency for several hundred nsec. Increasing the injected signal power to 5 W caused a substantial suppression of the gain spike. The observed spike suppression was significantly more than that predicted by the one-dimensional model analysis.
Nonlinear observer-based control of unstable wells (2008)

This paper presents a nonlinear observer-based control scheme applied to stabilize riser induced slugging. A simple empirical model is developed that describes the qualitative behavior of the downhole pressure in case of severe riser slugging. A nonlinear observer is developed for estimation of unmeasured states. The developed controller is designed by an integrator backstepping approach to stabilize the downhole pressure and eliminate riser slugging. Stabilization in the unstable region is demonstrated, and it is shown that the proposed controller not only can guarantee global stability, but also transient performance. Simulation results are presented to illustrate the effectiveness of proposed control scheme.
Tuning a riboswitch response through structural extension of a pseudoknot (2013)

Structural and dynamic features of RNA folding landscapes represent critical aspects of RNA function in the cell and are particularly central to riboswitch-mediated control of gene expression. Here, using single-molecule fluorescence energy transfer imaging, we explore the folding dynamics of the preQ1 class II riboswitch, an upstream mRNA element that regulates downstream encoded modification enzymes of queuosine biosynthesis. For reasons that are not presently understood, the classical pseudoknot fold of this system harbors an extra stem-loop structure within its 3'-terminal region immediately upstream of the Shine-Dalgarno sequence that contributes to formation of the ligand-bound state. By imaging ligand-dependent preQ1 riboswitch folding from multiple structural perspectives, we reveal that the extra stem-loop strongly influences pseudoknot dynamics in a manner that decreases its propensity to spontaneously fold and increases its responsiveness to ligand binding. We conclude that the extra stem-loop sensitizes this RNA to broaden the dynamic range of the ON/OFF regulatory switch.
RADIUS Dynamic Authorization Client MIB (2006)

functions that support the dynamic authorization extensions as defined in RFC 3576.
Characteristics of pressor response to endothelin in spontaneously hypertensive and Wistar-Kyoto rats. (1989)

Endothelin, an endothelium-derived vasoconstrictor peptide, and angiotensin II were intravenously injected into the femoral vein of normotensive Wistar-Kyoto (WKY) rats that had been anesthetized with urethane. Blood pressure and heart rate were recorded from a cannula inserted into the carotid artery. All experiments were carried out after treatment with adrenergic and cholinergic antagonists. Endothelin showed a potent, dose-dependent pressor action. The dose-response relations for the increase in blood pressure of rats receiving endothelin were comparable with those of rats receiving angiotensin II. However, endothelin showed far more long-lasting effects. Endothelin-induced responses consisted of three phases: a rapid and transient depressor phase and then two phases of pressor (transient and long-lasting) response. Nicardipine (0.1 mg/kg), a dihydropyridine Ca2+ channel blocker, markedly attenuated the slow phase of the pressor response but only slightly attenuated the rapid one. The pressor action of endothelin was not inhibited by continuous infusions of saralasin, which almost abolished the angiotensin II-induced pressor response. Endothelin-induced pressor response was also not attenuated by indomethacin, a prostaglandin synthesis inhibitor. These data provide evidence that endothelin produces a unique, potent, and long-lasting pressor response, which appears to be in part related to the activation of Ca2+ channels. In 12-week-old spontaneously hypertensive rats (SHR), the maximal pressor response to endothelin was slightly but significantly greater than that in age-matched WKY rats, but the dose dependency of the response was approximately consistent with that in WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Air drag on fine filaments at oblique and normal angles to the air stream (1994)

Abstract Measurements are reported for air drag on fine filaments whose axes are oriented at oblique and normal angles to the air velocity. In terms of the drag coefficient C DN the data are fit well by the following relation: C DN = 6.96( Re DN ) −0.440 ( d / d 0 ) 0.404 , where Re DN is the Reynolds number based on flow normal to the fiber axis, and d / d 0 is a dimensionless fiber diameter. A wide range of conditions were tested: filament diameters ranged from 13 to 390 microns, gas velocities ranged from 22 to 83 m/s, and fiber Reynolds numbers ranged from 29 to 2120.
Palladium-Catalyzed Carbonylative Transformation of C(sp<sup>3</sup>)–X Bonds (2014)

During the last 50 years, the palladium-catalyzed carbonylation reactions underwent continuous development. Apart from carbonylation of aromatic (pseudo)-halide and alkene (C-sp2) compounds, the use of C(sp3)–X compounds such as allyl compounds, benzyl compounds, and aliphatic alkanes have become the most useful tool for the synthesis of β,γ-unsaturated carbonyl compounds, aliphatic carboxylic acid, and their derivatives. The recently budding development in the area of palladium-catalyzed C(sp3)–X (especially X = H) activation makes us feel it necessary to file a summary on the past, current contributions, and a prospective outlook on the palladium-catalyzed carbonylative transformation of C(sp3)–X bonds, which is the focus of this review.
Dilute acid catalysed hydrolysis of cellulose – extension to formic acid (2012)

New methods are being sought for the production of chemicals, fuels and energy from renewable biomass. Lignocellulosic biomass consists mainly of cellulose, hemicellulose and lignin. Cellulose and hemicellulose can be converted to their building blocks, i.e. sugars, via hydrolysis. This thesis is focused on glucose production from cellulose by dilute acid hydrolysis. Acid hydrolysis has the drawback of limited glucose yields, but it has the potential to become a shortterm solution for biochemical production. During acid hydrolysis, the cellulose chain is split into glucose, which undergoes further decomposition reactions to hydroxymethylfurfural, levulinic acid, formic acid and by-products like insoluble humins. The present thesis aims to increase our knowledge on complicated acidcatalysed hydrolysis of cellulose. Glucose decomposition and cellulose hydrolysis were studied independently in laboratory experiments. Kinetic modelling was used as a tool to evaluate the results. The effect of the hydrogen ion on the reactions was evaluated using formic or sulphuric acid as a catalyst. This thesis provides new knowledge of cellulose hydrolysis and glucose decomposition in formic acid, a novel catalyst for high-temperature dilute acid hydrolysis. Glucose yields from cellulose hydrolysed in formic or in sulphuric acid were comparable, indicating that a weak organic acid could function as a cellulose hydrolysis catalyst. Biomass fibres in the form of wheat straw pulp were hydrolysed more selectively to glucose than a model component, microcrystalline cellulose, using formic acid. Glucose decomposition took place similarly in formic and sulphuric acid when the temperature dependence of the hydrogen ion concentration was taken into account, but a significant difference was found between the reaction rates of cellulose hydrolysis in formic acid and in sulphuric acid. The observations can be explained by changes in the cellulose hydrolysis mechanism. Thus, it is proposed in this thesis that side-reactions from cellulose to non-glucose compounds have a more significant role in the system than has earlier been understood.
Essential role for mevalonate synthesis in DNA replication (1979)

The relationship between 3-hydroxy-3-methylglutaryl (HMG) CoA reductase activity [mevalonate:NADP(+) oxidoreductase (CoA-acylating), EC 1.1.1.34] and DNA synthesis was studied in synchronized cultures of BHK-21 cells. During a 24-hr period of cell replication, two phases of accelerated thymidine incorporation into DNA corresponding to two S phases of the cell cycle occurred. A marked increase in activity of HMG CoA reductase was consistently observed at or just prior to each of these peaks of DNA synthesis. Moreover, when HMG CoA reductase activity was suppressed by the competitive inhibitor compactin, the normal S-phase burst of DNA synthesis was specifically and totally prevented. Finally, the compactin-induced inhibition of DNA synthesis could be completely reversed within minutes by the addition of mevalonate, the product of the HMG CoA reductase reaction. By contrast, addition of cholesterol-rich lipoproteins had no effect upon DNA synthesis in compactin-treated cells. These data demonstrate that HMG CoA reductase activity, and therefore the production of mevalonate, plays an essential role in the synthesis of DNA specifically during the S phase of the cell cycle. Moreover, the results indicate that this function of mevalonate in regulating DNA replication is independent of its conversion to cholesterol.
Constellation Shaping for Bit-Interleaved Coded APSK (2011)

This paper considers a technique for shaping a turbo-coded amplitude-phase shift keying (APSK) constellation. After bit-interleaving, a subset of the bits output by a binary turbo encoder are passed through a nonlinear shaping encoder. The bits at the output of the shaping encoder are more likely to be a zero than a one. These "shaping'' bits are interleaved and used to select from among a plurality of subconstellations, while the unshaped bits are used to select the symbol within the subconstellation. Symbols from lower-energy subconstellations are selected more frequently than those from higher-energy subconstellations. Information rates are computed for a variety of APSK and shaping code parameters, in an effort to optimize these parameters. It is found that, in theory, shaping gains of slightly over 0.3 dB may be achieved with 16-APSK and 32-APSK in AWGN, while the gains in ergodic Rayleigh fading are slightly lower. Simulation results show the bit error performance of the constellation-shaping strategy with an actual turbo code. The BER results suggest that gains significantly beyond 0.3 dB may be possible in AWGN when an iterative decoder is used, presumably due to the additional coding gain of the shaping code.
Infrared Photodetectors Based on Reduced Graphene Oxide and Graphene Nanoribbons (2011)

The use of reduced graphene oxide (RGO) and graphene nanoribbons (GNRs) as infrared photodetectors is explored, based on recent results dealing with solar cells, light-emitting devices, photodetectors, and ultrafast lasers. IR detection is demonstrated by both RGO and GNRs in terms of the time-resolved photocurrent and photoresponse. The responsivity of the detectors and their functioning are presented.
Regulation of mitophagy by the Gp78 E3 ubiquitin ligase (2013)

Glycoprotein 78 (Gp78) is a critical E3 ubiquitin ligase in endoplasmic reticulum-associated degradation. Overexpression of Flag-tagged Gp78 (Flag-gp78), but not Flag-gp78 mutated in its RING-finger domain (Flag-RINGmut) with deficient ubiquitin ligase activity, induces mitochondrial fragmentation and ubiquitination and proteasome-dependent degradation of the mitofusin (Mfn) mitochondrial fusion factors Mfn1/Mfn2. After mitochondrial depolarization with carbonyl cyanide m-chlorophenylhydrazone (CCCP), Flag-gp78 induced a threefold loss of depolarized mitochondria and significant loss of the inner mitochondrial protein OxPhosV. Flag-gp78-dependent loss of OxPhosV, but not Mfn1 or Mfn2, was prevented by small interfering RNA (siRNA) knockdown of the autophagy protein Atg5 in CCCP-treated cells. Gp78-induced mitophagy required ubiquitin ligase activity, as it is not observed upon transfection of Flag-RINGmut or cotransfection of Flag-gp78 with ubiquitin mutated at three critical lysine residues (K29, 48, 63R) involved in polyubiquitin chain elongation. Short hairpin RNA knockdown of Gp78 in HT-1080 fibrosarcoma cells increased mitofusin levels and reduced depolarization-induced mitophagy, whereas siRNA knockdown showed that Mfn1, but not Mfn2, was required for Gp78-dependent depolarization-induced mitophagy. Mitochondrial depolarization induced Gp78-dependent expression of the autophagic marker LC3II and recruitment of enhanced green fluorescent protein-LC3 to the Gp78- and calnexin-labeled, mitochondria-associated ER. Finally, Gp78-induced mitophagy is Parkin independent, as it occurs in Parkin-null HeLa cells and upon siRNA-mediated Parkin knockdown in HEK293 cells. This study therefore describes a novel role for the ER-associated Gp78 ubiquitin ligase and the Mfn1 mitochondrial fusion factor in mitophagy.
cSrc is a major cytosolic tyrosine kinase in vascular tissue (1999)

We are interested in identifying, in vascular tissue, nonreceptor tyrosine kinases that may be responsible for the contractile actions of G-protein-coupled agonists such as angiotensin II. By using a series of chromatographic steps, including ion exchange, hydrophobic, and affinity chromatography, we have isolated a major fraction of tyrosine kinase activity from the cytosolic fraction of porcine aorta tissue. According to (i) its immunologic cross-reactivity with the monoclonal anti-cSrc antibody, m327, and with the N-terminally directed monoclonal cSrc2-17 antibody, (ii) its inhibition by the C-terminal cSrc kinase, CSK, and (iii) its specificity for phosphorylating tyrosine 15 in the cdc2(6-20) peptide kinase substrate, we conclude that the kinase we have isolated represents porcine cSrc. A substantial proportion of the enzyme (>70%) was recovered in the cytoplasmic fraction from aorta tissue. The profile of inhibition of the human and porcine cSrc enzymes by a spectrum of tyrosine kinase inhibitors (PP 1 >> AG82 > AG490 congruent to genistein > AG10) was compared with the profile of inhibition of angiotensin II mediated contraction in a porcine coronary vascular preparation (AG10 >> genistein [Formula: see text] AG82 [Formula: see text] AG490; PP 1 inactive). The different inhibitory profiles indicated that cSrc does not represent the vascular tyrosine kinase responsible for the contractile actions of angiotensin II. We suggest, nonetheless, that cSrc plays a key role for other actions of angiotensin II in intact vascular tissue, such as the regulation of mitogen-activated protein kinase activity and gene transcription.Key words: tyrosine kinase, smooth muscle, cSrc.
Human‐Xenopus chimeras of G<sub>s</sub>α reveal a new region important for its activation of adenylyl cyclase (1994)

G proteins are heterotrimeric GTPases that play a key role in signal transduction. The alpha subunit of Gs bound to GTP is capable of activating adenylyl cyclase. The amino acid sequences derived from two X. laevis cDNA clones that apparently code for Gs alpha subunits are 92% identical to those found in the short form of human Gs alpha. Despite this high homology, the X. laevis Gs alpha clones expressed in vitro, yielded a protein that are not able to activate the adenylyl cyclase present in S49 cyc- membranes in contrast with human Gs alpha similarly expressed. This finding suggested that the few amino acid substitutions found in the amphibian subunit are important in defining the functionality of the human Gs alpha. The construction of chimeras composed of different fractions of the cDNAs of the two species was adopted as an approach in determining the regions of the molecule important in its functionality in this assay. Four pairs of chimeras were constructed using reciprocal combinations of the cDNAs coding for human and Xenopus Gs alpha. These eight constructs were expressed in vitro and equivalent amounts of the resulting proteins were assayed in the activation of adenylyl cyclase with GTP gamma and isoproterenol. The results obtained here clearly indicate that the G alpha sequence that extends from amino acid 70 to 140, is important for the functionality of human Gs alpha in activating adenylyl cyclase.
Plasma procalcitonin measured by time-resolved amplified cryptate emission (TRACE) in liver transplant patients. A prognosis marker of early infectious and non-infectious postoperative complications (2008)

Daily monitored PCT provides valuable information about the early outcome of OLTx.
Novel Tetracycline Resistance Determinant from the Oral Metagenome (2003)

A major drawback of most studies on how bacteria become resistant to antibiotics is that they concentrate mainly on bacteria that can be cultivated in the laboratory. In the present study, we cloned part of the oral metagenome and isolated a novel tetracycline resistance gene, tet(37), which inactivates tetracycline.
Improved method for blocking-artifact reduction in block coded images in wavelet-transform domain (2003)

The paper describes an approach for improving blocking-artifact reduction techniques. We purpose some simple processing methods in the wavelet transform domain that can reduce the blocking effects in block-coded images. The properties of block-coding make the errors appear in two categories: blocky noise, which causes blocking effects, and granular (non-blocky) noise. Once a degraded image is decomposed into subbands by wavelet filters, most energy of the blocky noise exists on the predetermined block boundaries of their corresponding subbands. We can reduce the blocky noise by using an averaging filter, a median filter, or the linear minimum mean square error in each subband. After the blocky noise is reduced, the granular noise can be further decreased. The approach was tested by applying it to images (Lena, cameraman). Results presented provide an improvement in the processed image.
Solid-state shear pulverization as a real-world process for polymer blends and nanocomposites (2007)

Solid-state shear pulverization (SSSP) is an innovative processing technique that has proven to effectively disperse nanoscale structural entities to achieve compatibilized polymer blends and exfoliated polymer nanocomposites. The SSSP apparatus, which is a modified twin-screw extruder, can continuously process polymer blends and nanocomposites without the use of heat, solvent, or chemical modifiers. For an insight into this unconventional process, the effects of different processing parameters are evaluated using several polystyrene-based blends as base systems. The manner by which the materials deform, mix, and disperse depend strongly on the type of polymers as well as the configuration of the mixing and pulverization zones in the SSSP apparatus. Such key processing variables as residence time and throughput are also considered and compared with typical values in conventional melt extrusion.
Descriptive epidemiological study of equine laminitis (1995)

A descriptive and matched case-control study of laminitis was conducted in 7 private practices and at the Texas Veterinary Medical Centre (TVMC) between May 1992 and July 1993. Out of 108 horses with laminitis, 19 acute (49%) and 20 chronic (51%) cases were seen in private practice and 16 acute (23%) and 53 (77%) cases at the TVMC. Gastrointestinal disease was the most common problem in 19/35 horses (54%), occurring just prior to the onset of acute laminitis in all hospitals. Among all horses in the study, most commonly used drugs were phenylbutazone (68%), acepromazine (34%), dimethyl sulphoxide (DMSO) (27%), antibiotics of various types (19%) and flunixin meglumine (19%). Acepromazine, DMSO and flunixin meglumine were used more commonly in acute cases of laminitis compared to chronic cases. In acutely affected horses, DMSO and flunixin meglumine were used significantly more often at the TVMC. In chronic cases, phenylbutazone and antibiotics were used more often in private practice. Shoeing and trimming were more commonly part of the treatment protocol for chronic cases. There were no significant associations between age, breed, sex or weight and the occurrence of acute laminitis. Horses with chronic laminitis were significantly older (P=0.04) and more females tended to be affected (P=0.08).