gebhart/patrepeval huggingface dataset:
Clinical Significance of Androgen Receptor Splice Variant-7 mRNA Detection in Circulating Tumor Cells of Men With Metastatic Castration-Resistant Prostate Cancer Treated With First- and Second-Line Abiraterone and Enzalutamide (2017)

Purpose We reported previously that the detection of androgen receptor splice variant-7 (AR-V7) mRNA in circulating tumor cells (CTCs) correlated with poor outcomes from the use of abiraterone and enzalutamide in patients with castration-resistant prostate cancer (CRPC). Here, we expanded our cohort size to better characterize the prognostic significance of AR-V7 in this setting. Methods We prospectively enrolled 202 patients with CRPC starting abiraterone or enzalutamide and investigated the prognostic value of CTC detection (+ v -) and AR-V7 detection (+ v -) using a CTC-based AR-V7 mRNA assay. We examined ≥ 50% prostate-specific antigen (PSA) responses, PSA progression-free survival, clinical and radiologic progression-free survival, and overall survival. We constructed multivariable models adjusting for PSA, Gleason sum, number of prior hormone therapies, prior abiraterone or enzalutamide use, prior taxane use, presence of visceral metastases, and Eastern Cooperative Oncology Group score. We also separately examined the first-line and second-line novel hormonal therapy (NHT) settings. Results Median follow-up times were 15.0, 21.7, and 14.6 months for CTC-, CTC+/AR-V7- and CTC+/AR-V7+ patients, respectively. CTC+/AR-V7+ patients were more likely to have Gleason scores ≥ 8 ( P = .05), metastatic disease at diagnosis ( P = .01), higher PSA ( P < .01), prior abiraterone or enzalutamide use ( P = .03), prior taxane use ( P = .02), and Eastern Cooperative Oncology Group ≥ 1 ( P = .01). Outcomes for the overall cohort (and separately for the first-line and second-line NHT cohorts) were best for CTC- patients, intermediate for CTC+/AR-V7- patients, and worse for CTC+/AR-V7+ patients. These correlations remained significant in multivariable models. Conclusion This expanded analysis further characterizes the importance of CTC-based AR-V7 mRNA detection in predicting outcomes in patients with CRPC receiving first- and second-line NHT and, to the best of our knowledge, is the first to suggest that this assay be interpreted using three separate prognostic categories: CTC-, CTC+/AR-V7-, and CTC+/AR-V7+.
COBRA VENOM FACTOR STIMULATES ANTI-??-GALACTOSE ANTIBODY PRODUCTION IN BABOONS (1996)

Cobra venom factor (CVF) depletes complement and may therefore be of use in preventing the hyperacute rejection that follows discordant organ xenotransplantation. In two baboons studied, the intramuscular injection of CVF (0.25 mg/kg) was followed by a marked reduction in serum C3 and CH50, and serum cytotoxicity to pig kidney (PK15) cells. There was, however, a very rapid rise in the level of anti-alpha-galactose (alpha Gal) antibody, and a slower rise in anti-CVF antibody. A second intramuscular injection of CVF on day 14 was ineffective in reducing C3, CH50, and serum cytotoxicity. The major oligosaccharide of CVF is known to contain alpha Gal residues, which we suggest stimulate the major increase in anti-alpha Gal antibody level seen in the present study. In the clinical situation, this might lead to an increased immune response to a concomitantly transplanted pig organ.
Interstitial cells of Cajal in enteric neurotransmission (2000)

Specialised cells known as interstitial cells of Cajal (ICCs), distributed in specific locations within the tunica muscularis of the gastrointestinal tract, serve as electrical pacemakers and mediators of enteric neurotransmission. Until recently, evidence to support a functional role of these cells has been, for the most part, indirect.
A phase I, pharmacokinetic (PK), and preliminary efficacy assessment of ALD518, a humanized anti-IL-6 antibody, in patients with advanced cancer (2009)

3025 Background: ALD518 is a humanized anti-IL-6 antibody being developed for the treatment of cancer cachexia and fatigue. The primary objective of the study was to determine the safety of ALD518. Methods: 9 patients (pts) with advanced cancer, ECOG 0–2, and C-reactive protein (CRP) &gt;10mg/L were enrolled. Pts were assigned to 1 of 3 dose-escalating cohorts (n=3/cohort). ALD518 was given as a single i.v. infusion of 80mg, 160mg, or 320mg. Pts were followed up for 12 weeks. Data included lab safety tests (LSTs), vital signs, ECGs, adverse events, hand grip strength (HGS), FACIT-F, PK and C-reactive protein (CRP). Results: 9 pts were evaluable for dose limiting toxicity (DLT) assessment at week 4 and 5/9 pts completed all visits. Of the 4 pts who failed to complete every visit; 3 were withdrawn due to progressive disease and 1 to be treated with chemotherapy. There were no DLTs or infusion reactions. There were 4 SAEs: 3 disease progressions and 1 sepsis secondary to a blocked biliary stent. There were no grade 3/4 toxicities. Changes in LSTs, CRP, HGS and FACIT-F fatigue subscale (pooled ITT analysis) are shown (Table). Conclusions: ALD518 given to pts with advanced cancer was safe and well tolerated. ALD518 reversed fatigue, increased hemoglobin and albumin, and there was a trend to increased HGS. There was a mild decrease in platelet count that remained stable throughout the study. [Table: see text] [Table: see text]
Upper‐Bounding the Incidence Rate of Associations Between Camouflage Uniforms and Surveillance Images* (2009)

Camouflage garments can be associated with surveillance images of a crime scene even in the absence of unique wear marks or very high-quality images. However, the probability of an accidental association, or incidence rate, is significant. The present work describes and validates a method for estimating the incidence rate based on a statistical model of the garment manufacturing process. The model was developed primarily for use with the current U.S. Army Combat Uniform (ACU), but can be applied to any camouflage garment. Eight garment manufacturers were studied, and all sources of variation in the manufacturing process were characterized. The marking and spreading procedures were found to be dominant and consistent sources of variation. However, some sources of variation, in particular those because of human operators, were not consistent enough to accurately characterize. Sources of variation that could not be well-characterized were ignored in the statistical model, yielding a worst-case estimate that is an upper-bound to the true incidence rate. The model was evaluated for a variety of cases. Depending on the quality of the surveillance image, the manufacturing parameters, and the local population, incidence rates range from about 3% to negligibly small. The model was validated by returning to one manufacturer, and sampling a large number of completed garments and estimating empirical match probabilities. The empirical probabilities validated the estimates of the worst-case incidence rate and also demonstrated that typical incidence rates are significantly lower.
Cellular mechanotransduction: putting all the pieces together again (2006)

Analysis of cellular mechanotransduction, the mechanism by which cells convert mechanical signals into biochemical responses, has focused on identification of critical mechanosensitive molecules and cellular components. Stretch-activated ion channels, caveolae, integrins, cadherins, growth factor receptors, myosin motors, cytoskeletal filaments, nuclei, extracellular matrix, and numerous other structures and signaling molecules have all been shown to contribute to the mechanotransduction response. However, little is known about how these different molecules function within the structural context of living cells, tissues, and organs to produce the orchestrated cellular behaviors required for mechanosensation, embryogenesis, and physiological control. Recent work from a wide range of fields reveals that organ, tissue, and cell anatomy are as important for mechanotransduction as individual mechanosensitive proteins and that our bodies use structural hierarchies (systems within systems) composed of interconnected networks that span from the macroscale to the nanoscale in order to focus stresses on specific mechanotransducer molecules. The presence of isometric tension (prestress) at all levels of these multiscale networks ensures that various molecular scale mechanochemical transduction mechanisms proceed simultaneously and produce a concerted response. Future research in this area will therefore require analysis, understanding, and modeling of tensionally integrated (tensegrity) systems of mechanochemical control.
Myxobacteria, producers of novel bioactive substances (2001)

Myxobacteria are soil bacteria that move by gliding and have an astonishing life cycle culminating in fruiting body formation. In a research program at the Gesellshaft für Biotechnologische Forschung over the past 25 years the organisms have been shown to be a rich source of potentially useful secondary metabolites. So far about 80 different basic compounds and 450 structural variants have been characterized. Many of those compounds were new. It is particularly remarkable that myxobacteria specialize in mechanisms of action that are very rare with other producers. Thus 20 new electron transport inhibitors, 10 substances that act on the cytoskeleton, four inhibitors of nucleic acid polymerases, and one inhibitor of fungal acetyl-CoA carboxylase, a novel mechanism of action, have been found.
KW-6002 (Kyowa Hakko Kogyo). (2001)

Kyowa Hakko is developing KW-6002, an adenosine A2A receptor antagonist, for the potential treatment of Parkinson's disease (PD) [183211]. The company subsequently began evaluating the compound for depression, and in June 2000 initiated a phase II trial for this indication. Good results have been obtained in a preclinical depression model and Kyowa Hakko hopes that KW-6002 will be representative of a new class of antidepressants [376107]. KW-6002 is undergoing phase II trials for PD in Japan [343257] and in Europe, including the UK 1271929], [321641], [402754]. As expected, KW-6002 entered phase II trials for PD in the US in October 1999 [321640], [342643], [360980], [402754]. The drug is of particular interest due to the absence of the involuntary movement adverse effects characteristic of L-DOPA therapy [271929]. Roche was to codevelop KW-6002 with Kyowa in the US and Europe, but withdrew from the development of this drug in April 1999 [321640]. Kyowa will continue with the drug's development in the US [321640]. NDAs are estimated to be filed around the end of 2001 and the drug is expected to be launched in Western Europe during 2002. An NDA is expected to be filed in Japan approximately three to four years later than in Western Europe [271929].
Capillary Electrophoresis–Mass Spectrometry in Metabolomics: The Potential for Driving Drug Discovery and Development (2013)

Metabolomics represents the global profiling of metabolites in a given biological system. It has been used to facilitate pharmaceutical discovery and development for over a decade. Advances in instrumentation have positioned capillary electrophoresis-mass spectrometry (CE-MS) as an important platform for both targeted and non-targeted metabolomics. In this mini-review covering the last five years, we focus on the latest development of CE-MS based metabolomics in (a) identification and validation of novel valuable therapeutic targets, (b) evaluation of drug efficacy, and (c) monitoring of drug unanticipated adverse effects. Some of the current issues and future directions of CE-MS metabolomics are also discussed in the end.
Injectable Bioglass as a Potential Substitute for Injectable Polytetrafluoroethylene (1992)

Injectable polytetrafluoroethylene (Teflon) and collagen have inherent problems that may prevent their long-term success. In search of a different injectable biomaterial we confirmed in rabbits the safety of injected Bioglass particles suspended in sodium hyaluronate. A second study was performed testing the ability of the Bioglass suspension to increase urethral resistance in pigs. Bioglass particles in suspension have the potential to substitute for polytetrafluoroethylene or collagen in the treatment of urinary incontinence or vesicoureteral reflux.
Cytosine Deaminase Gene as a Positive Selection Marker (1996)

Cytosine deaminase (EC 3.5.4.1), a non-mammalian enzyme, catalyzes the deamination of cytosine and 5-fluorocytosine to form uracil and 5-fluorouracil, respectively. Eukaryotic cells have been genetically modified with a bacterial cytosine deaminase gene to express a functional enzyme. When the genetically modified cells are combined with 5-fluorocytosine, it creates a potent negative selection system, which may have important applications in cancer gene therapy. In this paper, we introduce a novel positive selection method based upon the expression of the cytosine deaminase gene. This method utilizes inhibitors in the pyrimidine de novo synthesis pathway to create a condition in which cells are dependent on the conversion of pyrimidine supplements to uracil by cytosine deaminase. Thus, only cells expressing the cytosine deaminase gene can be rescued in a positive selection medium.
In vitro selection using a dual RNA library that allows primerless selection (2006)

High affinity target-binding aptamers are identified from random oligonucleotide libraries by an in vitro selection process called Systematic Evolution of Ligands by EXponential enrichment (SELEX). Since the SELEX process includes a PCR amplification step the randomized region of the oligonucleotide libraries need to be flanked by two fixed primer binding sequences. These primer binding sites are often difficult to truncate because they may be necessary to maintain the structure of the aptamer or may even be part of the target binding motif. We designed a novel type of RNA library that carries fixed sequences which constrain the oligonucleotides into a partly double-stranded structure, thereby minimizing the risk that the primer binding sequences become part of the target-binding motif. Moreover, the specific design of the library including the use of tandem RNA Polymerase promoters allows the selection of oligonucleotides without any primer binding sequences. The library was used to select aptamers to the mirror-image peptide of ghrelin. Ghrelin is a potent stimulator of growth-hormone release and food intake. After selection, the identified aptamer sequences were directly synthesized in their mirror-image configuration. The final 44 nt-Spiegelmer, named NOX-B11-3, blocks ghrelin action in a cell culture assay displaying an IC50 of 4.5 nM at 37 degrees C.
Sealed Gravitational Capillary Viscometry of Dimethyl Ether and Two Next-Generation Alternative Refrigerants (2012)

The viscosities of dimethyl ether (DME, C2H6O) and of the fluorinated propene isomers 2,3,3,3-tetrafluoroprop-1-ene (R1234yf, C3H2F4) and trans-1,3,3,3-tetrafluoropropene (R1234ze(E)) were measured in a combined temperature range from 242 K to 350 K at saturated liquid conditions. The instrument was a sealed gravitational capillary viscometer developed at NIST for volatile liquids. Calibration and adjustment of the instrument constant were conducted with n-pentane. The repeatability of the measurements was found to be approximately 1.5 %, leading to a temperature-dependent estimated combined standard uncertainty of the experimental data between 5.7 % at 242 K for dimethyl ether and 2.6 % at 340 K for R1234yf. The measurements were supplemented by ab initio calculations of the molecular size, shape, and charge distributions of the measured compounds. The viscosity results for dimethyl ether were compared with literature data. One other data set measured with a sealed capillary viscometer and exceeding the present results by up to 7 % could be reconciled by applying the vapor buoyancy correction. Then, all data agreed within the estimated uncertainty of the present results. Viscosities for the fluorinated propene isomers deviate up to 4 % from values predicted with the NIST extended corresponding-states model. The viscosities of the two isomers do not scale with their dipole moments. While the measured viscosity of R1234ze(E) with the lower dipole moment is close to that of R134a, the refrigerant to be replaced, that of R1234yf with the higher dipole moment is up to 25 % lower. The viscosity of dimethyl ether is compared with those of water and methanol.
Disparate Impact and Unfairly Discriminatory Insurance Rates (2009)

Historic actuarial literature, general insurance literature, and legislative histories reveal “unfairly discriminatory rates ” to be a cost-based concept. A rate structure is unfairly discriminatory if the insurance premium differences between insureds do not reasonably correspond to differences in expected insurance costs. More recently a new rate concept has arisen in some court cases which is referred to as “disparate impact ” (or “adverse impact”). Disparate impact has nothing to do with underlying insurance costs and is solely based on the disproportionate impact of the insurance rate structure on the insurance premiums paid by protected minority classes defined by race, color, religion, sex, or national origin. It would likely be a rare instance where the rate standard of unfairly discriminatory and the concept of disparate impact could be applied simultaneously to a risk classification plan without conflict. It is the author’s opinion that if the standard of disparate impact eventually prevails over the historical rate standard of unfairly discriminatory, then accurate risk assessment will be destroyed, adverse selection will be widespread in the insurance marketplace, and coverage availability will suffer.
The 16S rRNA binding site of Thermus thermophilus ribosomal protein S15: comparison with Escherichia coli S15, minimum site and structure. (1996)

Binding of Escherichia coli and Thermus thermophilus ribosomal proteins S15 to a 16S ribosomal RNA fragment from T. thermophilus (nt 559-753) has been investigated in detail by extensive deletion analysis, filter-binding assays, gel mobility shift, structure probing, footprinting with chemical, enzymatic, and hydroxyl radical probes. Both S15 proteins recognize two distinct sites. The first one maps in the bottom of helix 638-655/717-734 (H22) and in the three-way junction between helix 560-570/737-747 (H20), helix 571-600/606-634 (H21), and H22. The second is located in a conserved purine-rich region in the center of H22. The first site provides a higher contribution to the free energy of binding than the second one, and both are required for efficient binding. A short RNA fragment of 56 nt containing these elements binds S15 with high affinity. The structure of the rRNA is constrained by the three-way junction and requires both magnesium and S15 to be stabilized. A 3D model, derived by computer modeling with the use of experimental data, suggests that the bound form adopts a Y-shaped conformation, with a quasi-coaxial stacking of H22 on H20, and H21 forming an acute angle with H22. In this model, S15 binds to the shallow groove of the RNA on the exterior side of the Y-shaped structure, making contact with the two sites, which are separated by one helix turn.
Circuits, Signals, and Systems (1985)

These twenty lectures have been developed and refined by Professor Siebert during the more than two decades he has been teaching introductory Signals and Systems courses at MIT. The lectures are designed to pursue a variety of goals in parallel: to familiarize students with the properties of a fundamental set of analytical tools; to show how these tools can be applied to help understand many important concepts and devices in modern communication and control engineering practice; to explore some of the mathematical issues behind the powers and limitations of these tools; and to begin the development of the vocabulary and grammar, common images and metaphors, of a general language of signal and system theory. Although broadly organized as a series of lectures, many more topics and examples (as well as a large set of unusual problems and laboratory exercises) are included in the book than would be presented orally. Extensive use is made throughout of knowledge acquired in early courses in elementary electrical and electronic circuits and differential equations. Contents Review of the "classical" formulation and solution of dynamic equations for simple electrical circuits • The unilateral Laplace transform and its applications • System functions • Poles and zeros • Interconnected systems and feedback • The dynamics of feedback systems • Discrete-time signals and linear difference equations • The unilateral Z-transform and its applications • The unit-sample response and discrete-time convolution • Convolutional representations of continuous-time systems • Impulses and the superposition integral • Frequency-domain methods for general LTI systems • Fourier series • Fourier transforms and Fourier's theorem • Sampling in time and frequency • Filters, real and ideal • Duration, rise-time and bandwidth relationships: The uncertainty principle • Bandpass operations and analog communication systems • Fourier transforms in discrete-time systems • Random Signals • Modern communication systems Circuits, Signals, and Systems is included in The MIT Press Series in Electrical Engineering and Computer Science, copublished with McGraw-Hill.
Use of Dry Human and Bovine Amnion as a Biological Dressing (1981)

A new method of drying and sterilizing the amnion extends the life of the product to more than nine months and enables it to be stored at room temperature. The bovine amnion is unique and the first of its kind, there being no comparable series in the literature, to our knowledge. Bovine amnion has a large surface area and can provide bulk supplies. The membrane as prepared has been tested in 12 rabbits experimentally and in 70 patients of different ages with a variety of surgical lesions, mainly burns. More than 150 applications of the dried amnion have been made as the sole dressing for these patients. The results indicate that amnion, both human and bovine, is quite safe and effective as a biological dressing. The dried material retains all the physical and biological characteristics of the fresh membrane.
Design and Synthesis of a PSMA Inhibitor–Doxorubicin Conjugate for Targeted Prostate Cancer Therapy (2006)

Prostate-specific membrane antigen (PSMA) provides an attractive target for the development of targeted chemotherapeutics for prostate cancer. We have designed and synthesized a bioconjugate 1 that comprises the cytotoxic drug doxorubicin and one of our previously described urea-based PSMA inhibitors. While this bioconjugate retained high binding affinity for PSMA, it inhibited only 30 % of C4-2 cell growth at a concentration of 5.0 μM. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2452/2006/z500044_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.