gebhart/patrepeval huggingface dataset:
Abstract A208: Pharmacodynamic properties and antitumor efficacy of BI 836845, a fully human IGF ligand neutralizing antibody. (2011)

Abstract Insulin-like growth factor (IGF) signaling is thought to play an important role in the development of tumors and resistance to existing cancer therapies. The proliferative and pro-survival signals driven by the IGF ligands, IGF-1 and IGF-2, are transmitted through their binding to the IGF-1 receptor (IGF-1R). In addition, IGF-2 activates the insulin receptor variant A (IR-A) that is expressed during embryonic development as well as in many cancers. To target IGF signaling for cancer therapy we have developed BI 836845, a fully human IgG1 antibody derived from an antibody phage display library that can bind to and neutralize the functions of both IGF-1 and IGF-2. Surface plasmon resonance (Biacore) analysis demonstrated that BI 836845 has an affinity (KD) of 0.07 nM and 0.8 nM for human IGF-1 and IGF-2, respectively. BI 836845 also shows comparable affinities to mouse as well as rat IGF-1 and IGF-2, allowing a comprehensive pre-clinical characterization of the pharmacodynamic properties of the antibody in these species. Cell-based ELISA assays were used to demonstrate that BI 836845 potently neutralizes the ability of IGF-1 and IGF-2 to phosphorylate the human IGF-1R. Similarly, BI 836845 inhibits phosphorylation of IR-A driven by IGF-2. BI 836845 was also shown to completely and potently inhibit IGF bioactivity in human serum samples ex vivo. Pharmacodynamic effects of BI 836845 were studied in growing rats treated intravenously once weekly with 20, 60, or 200 mg/kg antibody. Inhibition of IGF bioactivity as determined by ex vivo IGF-1R phosphorylation potential in the plasma was observed at all dose levels, despite a corresponding increase in total IGF-1 levels. An increase in total IGF-1 levels has also been seen with IGF-1R targeted antibodies in clinical studies and is thought to be due to blockade of a growth hormone mediated physiological feedback mechanism. Treatment with BI 836845 resulted in a marked dose dependent reduction of rat body weight gain at all dose levels, consistent with the known role for IGFs in normal growth and development. BI 836845 potently inhibits the in vitro proliferation of cell lines derived from various cancers, with mesenchymal-derived cancer cell lines being particularly sensitive (EC50 values in the low nanomolar range). In a model of Ewing s sarcoma, using immunodeficient nude mice subcutaneously transplanted with human RD-ES cells, twice-weekly treatment with BI 836845 resulted in partial inhibition of tumor growth. Treatment in combination with rapamycin resulted in improved efficacy at tolerated doses. In conclusion, BI 836845 is a potent IGF ligand neutralizing antibody whose pharmacological profile warrants further investigation in clinical studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A208.
Gear Fault Detection in Rocket Engine Turbomachinery (2001)

A method for detecting anomalous gear behavior in rocket engine turbomachinery during acceptance hot e ring is presented. The diagnostic procedure is based on a cepstrum analysis of steady-state gearbox accelerations. In this application, the cepstrum is dee ned as the inverse discrete Fourier transform of the log of the two-sided autospectral density. The vibration measurements used in the analysis are acquired during static hot e re tests from accelerometers mounted on the external surface of the turbopump gearbox. Following the ground tests, the cepstrum technique is used to provide insight into the differences between turbopumps that have functioned nominally and those with out-of-family signatures. The effectiveness of the method is demonstrated by comparing analysisresultsfromanengineingoodconditionwith asimilarenginethatsufferedcompletegearfailureduringits development test. This example is used to suggest that the cepstrum method cannot only help detect out-of-family vibration characteristics, but can also provide insight into the nature of a defect. A source mechanism is proposed to explain the unique spectral characteristics that appear due to the presence of the gear fault.
Titanium Powder Metallurgy Products (1990)

Abstract This article focuses on the mechanical properties, production of titanium powder metallurgy (P/M) compacts, namely, blended elemental (BE) compacts and prealloyed (PA) compacts. It explains the postcompaction treatments of titanium P/M compacts, including heat treatment, and thermochemical processing. The article talks about the applications of titanium P/M products, namely, BE and PA products. It concludes with a short note on the future trends in titanium P/M technology.
UHF RiverSonde Streamflow Measurements at the Cowlitz River: Final Report (2005)

An extended field experiment was conducted from October 2003 through June 2004 using a CO-DAR RiverSonde UHF radar system at Castle Rock, Washington, USA on the Cowlitz River. A monostatic radar configuration on one bank of the river, with the antennas looking both upriver and downriver, provided high-quality data. Estimates of the along-channel velocity were made using least-squares fits of radial flow velocities in 5-m wide strips across the channel. The surface veloc-ity typically was about 1.0 m/s, but it reached nearly 3.5 m/s on 30 January 2004. Hourly means of the cross-channel profile were calculated for the entire experiment and were used to create a multi-month time series of mean velocity. The velocity time series was combined with a ground-penetrating radar measurement of the bottom profile and stage height to provide a time series of volume discharge. In addition to the UHF RiverSonde instrumentation, a weather station was installed in December 2003 and recorded wind, temperature, humidity and rainfall every ten minutes, and a video camera (a ”webcam”) periodically recorded images of the river and surrounding area. Also, several mi-crowave radar systems operated by the University of Washington were in operation within about
High resolution on-chip optical filter array based on double subwavelength grating reflectors (2015)

An optical filter array consisting of vertical narrow-band Fabry-Pérot (FP) resonators formed by two highly reflective high contrast subwavelength grating mirrors is reported. The filters are designed to cover a wide range of operation wavelengths (Δλ/λ = 5%) just by changing the in-plane grating parameters while the device thickness is maintained constant. Operation in the telecom band with transmission efficiencies greater than 40% and quality factors greater than 1,000 are measured experimentally for filters fabricated on the same substrate.
Substrate-Integrated Hollow Waveguides: A New Level of Integration in Mid-Infrared Gas Sensing (2013)

A new generation of hollow waveguide (HWG) gas cells of unprecedented compact dimensions facilitating low sample volumes suitable for broad- and narrow-band mid-infrared (MIR; 2.5-20 μm) sensing applications is reported: the substrate-integrated hollow waveguide (iHWG). iHWGs are layered structures providing light guiding channels integrated into a solid-state substrate material, which are competitive if not superior in performance to conventional leaky-mode fiber optic silica HWGs having similar optical pathlengths. In particular, the provided flexibility in device and optical design and the wide variety of manufacturing strategies, substrate materials, access to the optical channel, and optical coating options highlight the advantages of iHWGs in terms of robustness, compactness, and cost-effectiveness. Finally, the unmatched modularity of this novel waveguide approach facilitates tailoring iHWGs to almost any kind of gas sensor technology providing adaptability to the specific demands of a wide range of sensing scenarios. Device fabrication is demonstrated for the example of a yin-yang-shaped gold-coated iHWG fabricated within an aluminum substrate with a footprint of only 75 mm × 50 mm × 12 mm (L × W × H), yet providing a nominal optical absorption path length of more than 22 cm. The analytical utility of this device for advanced MIR gas sensing applications is demonstrated for the gaseous constituents butane, carbon dioxide, cyclopropane, isobutylene, and methane.
Measurement of thermal conductivity of polymer melts by the line‐source method (1990)

Abstract An apparatus has been developed for the measurement of thermal conductivity of polymer melts. Based on the transient “line source method,” it is ideally suited to these materials because measurements can be made quickly, before the onset of thermal degradation. Also, little or no sample preparation is required. A number of commercial polymers have been tested, including some glass‐fiber filled composites.
1723. MK-3866, a metallo-β-lactamase inhibitor, is not subject to efflux in <i>Pseudomonas aeruginosa</i> (2022)

Abstract Background Metallo-beta (β)-lactamases (MBLs) are in the class B group of β-lactamases due to zinc ions in the active site that are required for enzymatic activity. MK-3866 is a small molecule MBL inhibitor (MBLi) that restores antibacterial activity against resistant MBL-expressing gram-negative bacteria. Efflux is an important mechanism of antibiotic resistance in Pseudomonas aeruginosa (Pa). Imipenem (IMI) is not subject to efflux and neither is relebactam (REL), a β-lactamase inhibitor (BLi) of class A and C β-lactamases that is approved in combination with IMI/cilastatin. An efflux assay was devised to characterize MBLis for potentiation of IMI or cefepime (FEP) in isogenic strain pairs of efflux wild-type and multiply efflux deleted (MED) strains of Pa. Our objective was to determine if MK-3866 and related analogs are subject to efflux in Pa. Methods Bacterial isolates were engineered to demonstrate the ability of MBLis to be effluxed by introducing IMI metallo-β-lactamase-1 (IMP-1) (by electroporation) or Verona integron-encoded metallo-β-lactamases (VIM-1, VIM-2) (utilizing the cloning vector pFlp2) into isogenic MED and wild-type (WT) Pa isolates. Susceptibility testing was performed with IMI or FEP at a fixed concentration equal to the Pa Clinical and Laboratory Standards Institute susceptibility breakpoint for each and including a fixed 4 µg/mL of REL to inhibit class A or C enzymes, referred to as the SLICE assay. The concentration of MK-3866 and analogues required to restore susceptibility to either antibiotic in WT and MED strains was assessed. Results MICs to the combination of MK-3866/REL/IMI or MK-3866/REL/FEP vary by ≤4-fold between the WT and MED strain of each isogenic strain pair (Table 1). In contrast, large differential MIC values (efflux ratios) can be seen for the MK-3866 analogues A and B, with more moderate efflux ratios observed for other analogues. The exact efflux ratio depended on the MBL studied and the antibiotic partner. Conclusion MK-3866 showed a low potential for efflux whether IMP-1, VIM-1, or VIM-2 was expressed, in contrast to analogues of MK-3866 which exhibited differentials from nominal to extreme (≥ 128-fold) between efflux WT versus MED isolates. Disclosures Katherine Young, M.S., Merck & Co., Inc.: Stocks/Bonds Asra Mirza, MS, Merck & Co., Inc.: Stocks/Bonds Carl Balibar, PhD, Merck & Co., Inc.: Stocks/Bonds Shuzhi Dong, PhD, Merck & Co., Inc.: Stocks/Bonds Frank Bennett, PhD, Merck & Co., Inc.: Stocks/Bonds Jinlong Jiang, PhD, Merck & Co., Inc.: Stocks/Bonds Haiqun Tang, PhD, Merck & Co., Inc.: Stocks/Bonds Claire Tudge, PhD, Merck & Co., Inc.: Stocks/Bonds Jack Scott, PhD, Merck & Co., Inc.: Stocks/Bonds Dexi Yang, PhD, Merck & Co., Inc.: Stocks/Bonds Alexander Pasternak, PhD, Merck & Co., Inc.: Stocks/Bonds.
Defect-mediated surface morphology of nonpolar m-plane GaN (2007)

The role of extended defects in determining the atomic scale surface morphology of nonpolar {11¯00} m-plane gallium nitride has been elucidated. The heteroepitaxially grown m-GaN films are commonly reported to yield striated surface morphologies (slate morphology) correlated with their high densities of basal plane stacking faults. Here, the growth window was explored to allow nonslate morphologies for hydride vapor phase epitaxy. Lateral epitaxial overgrowth was then utilized to produce m-GaN films with three regimes of different extended defect contents. Elimination of stacking faults from the m-GaN yielded step-flow features with an average step height of 4–7 ML even for slate morphology growth conditions.
Molecular breast imaging using a dedicated high-performance instrument (2006)

In women with radiographically dense breasts, the sensitivity of mammography is less than 50%. With the increase in the percent of women with dense breasts, it is important to look at alternative screening techniques for this population. This article reviews the strengths and weaknesses of current imaging techniques and focuses on recent developments in semiconductor-based gamma camera systems that offer significant improvements in image quality over that achievable with single-crystal sodium iodide systems. We have developed a technique known as Molecular Breast Imaging (MBI) using small field of view Cadmium Zinc Telluride (CZT) gamma cameras that permits the breast to be imaged in a similar manner to mammography, using light pain-free compression. Computer simulations and experimental studies have shown that use of low-energy high sensitivity collimation coupled with the excellent energy resolution and intrinsic spatial resolution of CZT detectors provides optimum image quality for the detection of small breast lesions. Preliminary clinical studies with a prototype dual-detector system have demonstrated that Molecular Breast Imaging has a sensitivity of ~90% for the detection of breast tumors less than 10 mm in diameter. By comparison, conventional scintimammography only achieves a sensitivity of 50% in the detection of lesions < 10 mm. Because Molecular Breast Imaging is not affected by breast density, this technique may offer an important adjunct to mammography in the evaluation of women with dense breast parenchyma.
Human papillomavirus type 16 virus-like particles expressed in attenuated Salmonella typhimurium elicit mucosal and systemic neutralizing antibodies in mice (1997)

Attenuated strains of Salmonella are attractive live vaccine candidates for eliciting mucosal as well as systemic immune responses. The ability to induce immune responses in the reproductive tract may be critical for the effectiveness of a prophylactic vaccine against genital human papillomaviruses (HPV), which are important etiologic agents in the development of cervical cancer. To examine the potential of a live Salmonella-based vaccine to prevent genital HPV infection, the L1 major capsid protein from HPV type 16 (HPV16) was constitutively expressed in the PhoPc strain of Salmonella typhimurium. As demonstrated by electron microscopy, the L1 protein expressed in these bacteria assembled into virus-like particles (VLPs) that resemble authentic papillomavirus virions. This is the first demonstration that papillomavirus VLPs can self-assemble in prokaryotes. BALB/c mice were immunized with the HPV16 L1 recombinant PhoPc strain by the oral and nasal routes. Despite a low stability of the L1-expressing plasmid in vivo, a double nasal immunization was effective in inducing L1-specific serum antibodies that recognized mainly native, but not disassembled, VLPs. These antibodies effectively neutralized HPV16 pseudotyped virions in an in vitro infectivity assay. Conformationally dependent anti-VLP immunoglobulin A (IgA) and IgG were also detected in oral and vaginal secretions, indicating that potentially protective antibody responses were elicited at mucosal sites. Recombinant attenuated Salmonella expressing HPV capsids may represent a promising vaccine candidate against genital HPV infection.
A facile and efficient synthesis of d<sub>6</sub>‐labeled PU‐H71, a purine‐scaffold Hsp90 inhibitor (2009)

Abstract PU‐H71 is a purine‐scaffold Hsp90 inhibitor currently undergoing late stage preclinical evaluation for the treatment of cancer. In this investigation, we present a simple method for the synthesis of d 6 ‐labeled PU‐H71 for use as an internal standard to accurately quantitate the drug in biological matrices based on an LC‐MS‐MS method. PU‐H71‐d 6 was synthesized in five steps using readily available 1,3‐dibromopropane‐d 6 and is an important compound for the advancement of our clinical program. Copyright © 2009 John Wiley & Sons, Ltd.
Virtual Reality in Dementia Diseases (2019)

Most medical research that related to detection and training patients with dementia diseases are based on the traditional clinic tests with high cost devices in hospitals such as Magnetic Resonance Imaging (MRI). Accordingly, there is an expanding requirement for utilizing automated techniques in dementia's to completely use the advantages circumstances by advanced innovations. Subsequently, it was fitting to investigate the more current, more successful applications that receiving the psychological techniques with automated strategies. One of the techniques depends on virtual conditions which are given extra aces to psychological test and permit patients to immersive in a controlled domain. This paper proposed a serious game, intellectual electronic test for assessment of dementia's patients dependent on 3D virtual environments platform.
A 3.3-V single power supply 16-Mb nonvolatile virtual DRAM using a NAND flash memory technology (1997)

A 3.3-V 16-Mb nonvolatile memory having operation virtually identical to DRAM with package pin compatibility has been developed. Read and write operations are fully DRAM compatible except for a longer RAS precharge time after write. Fast random access time of 63 ns with the NAND flash memory cell is achieved by using a hierarchical row decoder scheme and a unique folded bit-line architecture which also allows bit-by-bit program verify and inhibit operation. Fast page mode with a column address access time of 21 ns is achieved by sensing and latching 4 k cells simultaneously. To allow byte alterability, nonvolatile restore operation with self-contained erase is developed. Self-contained erase is word-line based, and increased cell disturb due to the word-line based erase is relaxed by adding a boosted bit-line scheme to a conventional self-boosting technique. The device is fabricated in a 0.5-/spl mu/m triple-well, p-substrate CMOS process using two-metal and three-poly interconnect layers. A resulting die size is 86.6 mm/sup 2/, and the effective cell size including the overhead of string select transistors is 2.0 /spl mu/m/sup 2/.
CC chemokine ligand 7 expression in liver metastasis of colorectal cancer (2012)

The main cause of death for colorectal cancer (CRC) patients is the development of metastatic lesions at sites distant from the primary tumor. Therefore, it is important to find biomarkers that are related to the metastasis and to study the possible mechanisms. Recent data have shown that soluble attractant molecules called chemokines support the metastasis of certain cancers to certain organs. To identify molecular regulators that are differentially expressed in liver metastasis of CRC, PCR array analysis was performed and CC chemokine ligand 7 (CCL7) showed remarkable overexpression in liver metastatic tumor tissues. To validate the results of the PCR array, 30 patients with primary CRC and liver metastases were selected. Immunohistochemistry and real-time PCR analysis showed that CCL7 was expressed in normal colonic epithelium and the expression was higher in liver metastases compared to primary CRC (p<0.001). Real-time PCR showed that the expression of CCR1, CCR2 and CCR3 was also higher in liver metastases compared to primary CRC (p=0.001, p=0.033 and p<0.001, respectively). In conclusion, correlation of CCL7 overexpression and its receptor expression with colon cancer liver metastasis suggests that CCL7 as a novel target in liver metastasis of CRC may be of potential clinical value for the prevention of hepatic recurrences.
Electroless Platinum Deposition Using Co3+/Co2+ Redox Couple as a Reducing Agent (2021)

In the present work, the kinetics of electroless deposition of Pt, using a cobalt ion redox system (Co<sup>3+</sup>/Co<sup>2+</sup>) as a reducing agent, has been investigated. The deposition rate of Pt depends on the pH, concentration of reactants, and temperature. The deaeration and bubbling of the plating solution with argon play an essential role. It was found that 0.11 mg cm<sup>-2</sup> of Pt films could be deposited on the surface of a roughed glass sheet in one hour without replenishing the solution. Additional data have been obtained on the grounds of electrochemical quartz crystal microbalance experiments. The bubbling (agitation) of the electroless Pt plating solution with argon during the deposition of Pt results in a higher deposition rate and is ca. 3 µg cm<sup>-2</sup> min<sup>-1</sup>. The Pt deposition rate is far less, and is as low as 0.14 µg cm<sup>-2</sup> min<sup>-1</sup> when the electroless Pt plating solution is not bubbled with argon during the deposition of Pt.
CO.sub.2 laser (1977)

The disclosure relates to a pulsed gas laser comprising an optical resonant cavity, a CO.sub.2 lasing medium, structure for containing the CO.sub.2 lasing medium within the optical cavity and a device for causing a population inversion in the lasing medium, with a novel improvement comprising structure for causing a laser pulse comprising a wavelength in the near 14 .mu.m and near 16 .mu.m range. The structure for cooling the CO.sub.2 lasing medium to less than about -40.degree. C as well is a structure for pumping the maximum inversion of CO.sub.2 molecules within the lasing medium by minimizing the population in the 010 level.
Revisiting the STEC Testing Approach: Using espK and espV to Make Enterohemorrhagic Escherichia coli (EHEC) Detection More Reliable in Beef (2016)

Current methods for screening Enterohemorrhagic Escherichia coli (EHEC) O157 and non-O157 in beef enrichments typically rely on the molecular detection of stx, eae, and serogroup-specific wzx or wzy gene fragments. As these genetic markers can also be found in some non-EHEC strains, a number of "false positive" results are obtained. Here, we explore the suitability of five novel molecular markers, espK, espV, ureD, Z2098, and CRISPRO26:H11 as candidates for a more accurate screening of EHEC strains of greater clinical significance in industrialized countries. Of the 1739 beef enrichments tested, 180 were positive for both stx and eae genes. Ninety (50%) of these tested negative for espK, espV, ureD, and Z2098, but 12 out of these negative samples were positive for the CRISPRO26:H11 gene marker specific for a newly emerging virulent EHEC O26:H11 French clone. We show that screening for stx, eae, espK, and espV, in association with the CRISPRO26:H11 marker is a better approach to narrow down the EHEC screening step in beef enrichments. The number of potentially positive samples was reduced by 48.88% by means of this alternative strategy compared to the European and American reference methods, thus substantially improving the discriminatory power of EHEC screening systems. This approach is in line with the EFSA (European Food Safety Authority) opinion on pathogenic STEC published in 2013.
Pharmacokinetics of levosimendan and its circulating metabolites in patients with heart failure after an extended continuous infusion of levosimendan (2004)

The metabolites of levosimendan, OR-1855 and OR-1896, were formed and eliminated slowly, their peak concentrations occurring after termination of the 7-day infusion of the drug.