gebhart/patrepeval huggingface dataset:
Class III β-Tubulin Expression Predicts Prostate Tumor Aggressiveness and Patient Response to Docetaxel-Based Chemotherapy (2010)

Expression of class III β-tubulin (βIII-tubulin) correlates with tumor progression and resistance to taxane-based therapies for several human malignancies, but its use as a biomarker of tumor behavior in prostate cancer (PCa) remains largely unexplored. Here, we describe βIII-tubulin immunohistochemical staining patterns of prostate tumors obtained from a broad spectrum of PCa patients, some of whom subsequently received docetaxel therapy for castration-resistant PCa (CRPC). Elevated βIII-tubulin expression was significantly associated with tumor aggressiveness in PCa patients with presumed localized disease, as it was found to be an independent marker of biochemical recurrence after treatment. Additionally, βIII-tubulin expression in tumor cells was an independent predictor of lower overall survival for patients receiving docetaxel-based chemotherapy for CRPC. Manipulation of βIII-tubulin expression in human PCa cell lines using a human βIII-tubulin expression vector or βIII-tubulin small interfering RNA altered cell survival in response to docetaxel treatment in a manner that supports a role for βIII-tubulin expression as a mediator of PCa cell resistance to docetaxel therapy. Our findings suggest a role for βIII-tubulin as candidate theranostic biomarker to predict the response to docetaxel-based chemotherapy as well as to target for treatment of docetaxel-resistant CRPC.
In Vitro and In Vivo Evaluation of Cysteine and Site Specific Conjugated Herceptin Antibody-Drug Conjugates (2014)

Antibody drug conjugates (ADCs) are monoclonal antibodies designed to deliver a cytotoxic drug selectively to antigen expressing cells. Several components of an ADC including the selection of the antibody, the linker, the cytotoxic drug payload and the site of attachment used to attach the drug to the antibody are critical to the activity and development of the ADC. The cytotoxic drugs or payloads used to make ADCs are typically conjugated to the antibody through cysteine or lysine residues. This results in ADCs that have a heterogeneous number of drugs per antibody. The number of drugs per antibody commonly referred to as the drug to antibody ratio (DAR), can vary between 0 and 8 drugs for a IgG1 antibody. Antibodies with 0 drugs are ineffective and compete with the ADC for binding to the antigen expressing cells. Antibodies with 8 drugs per antibody have reduced in vivo stability, which may contribute to non target related toxicities. In these studies we incorporated a non-natural amino acid, para acetyl phenylalanine, at two unique sites within an antibody against Her2/neu. We covalently attached a cytotoxic drug to these sites to form an ADC which contains two drugs per antibody. We report the results from the first direct preclinical comparison of a site specific non-natural amino acid anti-Her2 ADC and a cysteine conjugated anti-Her2 ADC. We report that the site specific non-natural amino acid anti-Her2 ADCs have superior in vitro serum stability and preclinical toxicology profile in rats as compared to the cysteine conjugated anti-Her2 ADCs. We also demonstrate that the site specific non-natural amino acid anti-Her2 ADCs maintain their in vitro potency and in vivo efficacy against Her2 expressing human tumor cell lines. Our data suggests that site specific non-natural amino acid ADCs may have a superior therapeutic window than cysteine conjugated ADCs.
Investigation ofin-vitrorelease characteristics of NSAID-loaded polylactic acid microspheres (1996)

The intra-pulmonary delivery of non-steroidal anti-inflammatory drug-loaded PLA microspheres has potential utility in the treatment of inflammatory lung conditions such as asthma. Drug encapsulation efficiency and release kinetics depend upon a variety of parameters in the production process, all of which affect the properties of the microspheres produced. The release of piroxicam from PLA microspheres followed an apparently biphasic release profile. PLA microspheres containing indomethacin, however, exhibited kinetics which approached more closely to zero order release. The effect of microsphere production parameters upon these release profiles has been investigated. Results indicate that factors affecting the nature of the microsphere matrix have the greatest influence on release profiles. The use of halothane as organic solvent in the microsphere production increases the burst release effect. Residual halothane is known to be present in the microspheres, producing a less stable matrix, thus allowing much faster release of the drug. The nature of drug incorporated also appears to affect the nature of the microspheres matrix. Piroxicam-loaded microspheres possess a much more porous matrix than indomethacin-loaded microspheres, as evidenced by washing procedures. This difference could explain the difference in release profiles between the two types of microspheres.
Testosterone inhibits osteoclast formation stimulated by parathyroid hormone through androgen receptor (2001)

Androgens play an important role in the regulation of bone metabolism in animals and humans. The present study was performed to investigate whether androgens would affect osteoclast formation stimulated by parathyroid hormone (PTH) in mouse bone cell cultures and its mechanism. Testosterone as well as alpha-dihydrotestosterone (DHT) concentration-dependently inhibited osteoclast formation induced by PTH-(1-34). 10(-8) M ICI 182780, an estrogen receptor inhibitor, did not affect PTH-induced osteoclast formation antagonized by 10(-8) M testosterone, although it completely antagonized the effects of 10(-8) M 17beta-estradiol. Moreover, 3 microM 4-androsten-4-ol-3,17-dione, an aromatase inhibitor, did not affect PTH-induced osteoclast formation antagonized by testosterone. Hydroxyflutamide, an androgen receptor antagonist, concentration-dependently antagonized the inhibitory effects of testosterone as well as DHT on PTH-stimulated osteoclast formation. In conclusion, the present study first demonstrated that testosterone inhibited osteoclast formation stimulated by PTH through the androgen receptor, but not through the production of intrinsic estrogen in mouse bone cell cultures.
Inlet Conditions for Image-Based CFD Models of the Carotid Bifurcation: Is it Reasonable to Assume Fully Developed Flow? (2006)

The degree of variation is demonstrated to be within the range of the other computational assumptions, and we conclude that given a sufficient entrance length of realistic geometry, simplification to fully developed axial (i.e., Womersley) flow may be made without penalty. Thus, given a choice between measuring three components of inlet velocity or a greater geometric extent, we recommend effort be given to more accurate and detailed geometric reconstructions, as being of primary influence on physiologically significant indicators.
Near Infrared Photoimmunotherapy Targeting EGFR Positive Triple Negative Breast Cancer: Optimizing the Conjugate-Light Regimen (2015)

NIR-PIT for TNBC was effective regardless of expression of EGFR, however, greater cell killing was shown with higher EGFR expression tumor in vitro. In all treatment regimens, NIR-PIT suppressed tumor growth, resulting in significantly prolonged survival that further improved by splitting the APC dose and using repeated light exposures.
Effect of Nitrogen Fertilizer on Yield, Size, and Color of ‘Golden Delicious’ Apple1 (1974)

Abstract Fruit color and quality of ‘Golden Delicious’ apples was directly related to the nitrogen content of the tree. When leaf-nitrogen (N) levels were above 2.2% dry weight, the fruit tended to be large and green. Maximum yields of high-quality fruit were obtained when leaf-N levels were from 1.9 to 2.1% dry weight.
Medications for treating alcohol dependence. (2005)

Medications for treating alcohol dependence primarily have been adjunctive interventions, and only three medications--disulfiram, naltrexone, and acamprosate--are approved for this indication by the U.S. Food and Drug Administration. Disulfiram, an aversive agent that has been used for more than 40 years, has significant adverse effects and compliance difficulties with no clear evidence that it increases abstinence rates, decreases relapse rates, or reduces cravings. In contrast, naltrexone, an anticraving agent, reduces relapse rates and cravings and increases abstinence rates. Acamprosate also reduces relapse rates and increases abstinence rates. Serotonergic and anticonvulsant agents promise to play more of a role in the treatment of alcohol dependence. Although not approved by the U.S. Food and Drug Administration for this indication, the anticonvulsant topiramate and several serotonergic agents (e.g., fluoxetine, ondansetron) have been shown in recent studies to increase abstinence rates and decrease drinking.
A discrete multitone power line communications system (2002)

In-building power lines have been considered as a medium for high speed data transmission for applications like home networking and Internet access. Frequency selectivity and time variation of this medium in addition to the high level of narrow-band and impulsive interference makes multi-carrier modulation, and especially its popular variant discrete multitone (DMT), an attractive modulation candidate for this application. This paper presents the results of our measurements of the high frequency characteristics of ordinary in-building power lines, as well as simulation results of a DMT transceiver system in an in-building power line environment.
Code coverage testing using hardware performance monitoring support (2005)

Code coverage analysis, the process of finding code exercised by a particular set of test inputs, is an important component of software development and verification. Most traditional methods of implementing code coverage analysis tools are based on program instrumentation. These methods typically incur high overhead due to the insertion and execution of instrumentation code, and are not deployable in many software environments. Hardware-based sampling techniques attempt to lower overhead by leveraging existing Hardware Performance Monitoring (HPM) support for program counter (PC) sampling. While PC-sampling incurs lower levels of overhead, it does not provide complete coverage information. This paper extends the HPM approach in two ways. First, it utilizes the sampling of branch vectors which are supported on modern processors. Second, compiler analysis is performed on branch vectors to extend the amount of code coverage information derived from each sample. This paper shows that although HPM is generally used to guide performance improvement efforts, there is substantial promise in leveraging the HPM information for code debugging and verification. The combination of sampled branch vectors and compiler analysis can be used to attain upwards of 80% of the actual code coverage.
Unexpected genomic rearrangements at targeted loci associated with CRISPR/Cas9-mediated knock-in (2019)

The CRISPR/Cas9 gene editing tool enables accessible and efficient modifications which (re)ignited molecular research in certain species. However, targeted integration of large DNA fragments using CRISPR/Cas9 can still be challenging in numerous models. To systematically compare CRISPR/Cas9's efficiency to classical homologous recombination (cHR) for insertion of large DNA fragments, we thoroughly performed and analyzed 221 experiments targeting 128 loci in mouse ES cells. Although both technologies proved efficient, CRISPR/Cas9 yielded significantly more positive clones as detected by overlapping PCRs. It also induced unexpected rearrangements around the targeted site, ultimately rendering CRISPR/Cas9 less efficient than cHR for the production of fully validated clones. These data show that CRISPR/Cas9-mediated recombination can induce complex long-range modifications at targeted loci, thus emphasizing the need for thorough characterization of any genetically modified material obtained through CRISPR-mediated gene editing before further functional studies or therapeutic use.
A New Route to Thio- and Selenosulfonates from Disulfides and Diselenides. Application to the Synthesis of New Thio- and Selenoesters of Triflic Acid (1996)

Alkyl and aryl trifluoromethanethiosulfonates(1) (or selenosulfonates) were prepared in one step either from alkyl and aryl sulfenyl (or selenenyl) chlorides and sodium trifluoromethanesulfinate (3) or, more generally, from disulfides (or diselenides), 3, and bromine. The second method involved trifluoromethanesulfonyl bromide as key intermediate. Benzenethiosulfonates were obtained in a similar way from disulfides, benzenesulfinate, and bromine but benzeneselenosulfonates could not be obtained by the same method from diselenides.
Acupuncture for migraine prophylaxis (2009)

In the previous version of this review, evidence in support of acupuncture for migraine prophylaxis was considered promising but insufficient. Now, with 12 additional trials, there is consistent evidence that acupuncture provides additional benefit to treatment of acute migraine attacks only or to routine care. There is no evidence for an effect of 'true' acupuncture over sham interventions, though this is difficult to interpret, as exact point location could be of limited importance. Available studies suggest that acupuncture is at least as effective as, or possibly more effective than, prophylactic drug treatment, and has fewer adverse effects. Acupuncture should be considered a treatment option for patients willing to undergo this treatment.
A non-heme iron protein with heme tendencies: An investigation of the substrate specificity of thymine hydroxylase (1993)

Thymine hydroxylase from Rhodotorula glutinis catalyzes the oxidation of thymine to its alcohol, aldehyde, and carboxylic acid in three successive reactions. Each step involves stoichiometric consumption of O2 and alpha-ketoglutarate and formation of CO2 and succinate. Given the promiscuity of this enzyme, it was hoped that it would serve as a prototype for understanding the mechanism of this class of enzymes, the non-heme Fe2+ dioxygenases. Kinetic parameters for thymine, O2, Fe2+, and alpha-ketoglutarate have been determined, and isotope effect analysis of (trideuteriomethyl)thymine with enzyme reveals D(V) = 2.08 and D(V/K) = 1.11 at saturating O2. The kinetic parameters for (hydroxymethyl)uracil oxidation have been determined, and incubation of (5'-R)- and (5'-S)-[5'-2H]-5-(hydroxymethyl)uracil with enzyme reveals stereospecific removal of the pro-S hydrogen. No apparent isotope effect is observed in this reaction. The substrate specificity of this enzyme has been examined in detail. The enzyme can catalyze epoxidation, oxidation of a thioether to a sulfoxide and a sulfone, hydroxylation of an unactivated carbon-hydrogen bond, and oxidation of a methylamine to formaldehyde, as revealed through studies with 5-vinyluracil, 5-(methylthio)uracil, 5,6-dihydrothymine, and 1-methylthymine, respectively. In each case, the products were identified by gas chromatography-mass spectrometry, and 18O2-labeling studies revealed that one atom from O2 is incorporated into each product. The enzyme has also been shown to catalyze an uncoupling of hydroxylation and decarboxylation in the presence of a substrate analog incapable of undergoing hydroxylation or a substrate that is difficult to oxidize.(ABSTRACT TRUNCATED AT 250 WORDS)
Epithelium-on photorefractive intrastromal cross-linking (PiXL) for reduction of low myopia (2017)

This paper serves to introduce and report the early clinical results of epithelium-on PiXL, a novel application of cornea cross-linking, in reducing low myopia in Asian eyes, which are under-represented in studies of similar design.
Stimulating Unconventional Reservoirs: Lessons Learned, Successful Practices, Areas for Improvement (2008)

Abstract The term "unconventional reservoir" has different meanings to different people. Certain reservoirs termed unconventional have a rock matrix consisting of inter-particle pore networks with very small pore connections imparting very poor fluid-flow characteristics. Abundant volumes of oil or gas can be stored in these rocks, and often the rock is high in organic content and the source of the hydrocarbon. Yet because of marginal rock matrix quality, these reservoirs generally require both natural and induced fracture networks to enable economic recovery of the hydrocarbon. Rock types in this class include shale and coalbed methane (CBM.) The term shale is a catchall for any rock consisting of extremely small framework particles with minute pores charged with hydrocarbon and includes carbonate and quartz-rich rocks. Another type of unconventional reservoir is stacked pay units exhibiting somewhat better pore characteristics than in the case outlined above but with the individual units tending to be lenticular in shape and having an extremely small size or volume. These two classes of unconventional reservoirs are amenable to well stimulation and will be the focus of this paper. The above rock types when commercially exploited are known as resource plays. Once a low-priority, the depletion of conventional reservoirs and improving price for oil and gas has driven unconventional reservoirs to an important place in the oil and gas industry. In some regions (i.e., Rocky Mountain province), unconventional reservoirs represent the primary target of current activity and remaining hydrocarbon development. Given their unique petrophysical properties, each type of unconventional reservoir requires a unique approach to well stimulation, with often differing objectives than exist with conventional reservoir types. This paper reviews the characteristics of the basic unconventional reservoir types, lessons learned and successful stimulation practices developed in completing these reservoirs, and areas for improvement in treatment and reservoir characterization and treatment design.
A two-stage intelligent model to extract features from PPG for drowsiness detection (2016)

This paper presented a two-stage intelligent model that combined the wavelet packet transform (WPT) and functional-link-based fuzzy neural network (FLFNN) to access drowsy level. Early detection of drowsiness can help prevent drivers from involving in car accidents. According to the report of U.S. National Highway Traffic Safety Administration, drivers falling asleep while driving were responsible for at least 100,000 automobile crashes annually that resulted in an annual average of 40,000 non-fatal injuries and 1,550 fatalities [3]. Furthermore, the National Sleep Foundation had reported that 60% of adult drivers drove with drowsy and 37% of them had eventually fallen asleep during driving [4]. The fact behind those reports indicated that there is a dire need to develop a sensor device that detects drowsy status at an early stage.
Interleukin 4: Signalling Mechanisms and Control of T Cell Differentiation (2007)

Interleukin 4 (IL-4) is a pleiotropic type I cytokine that controls both growth and differentiation among haemopoietic and non-haemopoietic cells. Its receptor is a heterodimer. One chain, the IL-4R alpha chain, binds IL-4 with high affinity and determines the nature of the biochemical signals that are induced. The second chain, gamma c, is required for the induction of such signals. IL-4-mediated growth depends upon activation events that involve phosphorylation of Y497 of IL-4R alpha, leading to the binding and phosphorylation of 4PS/IRS-2 in haemopoietic cells and of IRS-1 in non-haemopoietic cells. By contrast, IL-4-mediated differentiation events depend upon more distal regions of the IL-4R alpha chain that include a series of STAT-6 binding sites. The distinctive roles of these receptor domains was verified by receptor-reconstruction experiments. The 'growth' and 'differentiation' domains of the IL-4R alpha chain, independently expressed as chimeric structures with a truncated version of the IL-2R beta chain, were shown to convey their functions to the hybrid receptor. The critical role of STAT-6 in IL-4-mediated gene activation and differentiation was made clear by the finding that lymphocytes from STAT-6 knockout mice are strikingly deficient in these functions but have retained the capacity to grow, at least partially, in response to IL-4. IL-4 plays a central role in determining the phenotype of naive CD4+ T cells. In the presence of IL-4, newly primed naive T cells develop into IL-4 producers while in its absence they preferentially become gamma-interferon (IFN-gamma) producers. Recently, a specialized subpopulation of T cells, CD4+/NK1.1+ cells, has been shown to produce large amounts of IL-4 upon stimulation. Two examples of mice with deficiencies in these cells are described--beta 2-microglobulin knockout mice and SJL mice. Both show defects in the development of IL-4-producing cells and in the increase in serum IgE in response to stimulation with the polyclonal stimulant anti-IgD. Both sets of mice have major diminutions in the number of CD4+/ NK1.1+ T cells, strongly indicating an important role of these cells in some but not all IgE responses to physiologic stimuli.
Inhibition of glial scarring in the injured rat brain by a recombinant human monoclonal antibody to transforming growth factor‐β2 (1999)

The transforming growth factor-betas (TGF-betas) are potent fibrogenic factors implicated in numerous central nervous system (CNS) pathologies in which fibrosis and neural dysfunction are causally associated. In this study, we aim to limit the fibrogenic process in a model of CNS scarring using a recombinant human monoclonal antibody, derived from phage display libraries and specific to the active form of the TGF-beta2 isoform. The implicit inference of the work was that, as such antibodies are potential pharmacological agents for the treatment of human CNS fibrotic diseases, validation of efficacy in a mammalian animal model is a first step towards this end. Treatment of cerebral wounds with the anti-TGF-beta2 antibody led to a marked attenuation of all aspects of CNS scarring, including matrix deposition, formation of an accessory glial-limiting membrane, inflammation and angiogenesis. For example, in the wound, levels of: (i) the connective tissue components fibronectin, laminin and chondroitin sulphate proteoglycan; and (ii) wound-responsive cells including astrocytes and macrophages/microglia, were markedly reduced. Our findings suggest that such synthetic anti-fibrotic TGF-beta antibodies are potentially applicable to a number of human CNS fibrotic diseases to arrest the deposition of excessive extracellular matrix components, and maintain and/or restore functional integrity.