gebhart/patrepeval huggingface dataset:
Pharmacokinetics of (-)-2'-3'-dideoxy-3'-thiacytidine in woodchucks (1996)

The woodchuck (Marmota monax) has proven to be a suitable animal model for studying hepatitis B virus (HBV) infection owing to similarities in the course of infection between woodchuck hepatitis virus (WHV) in woodchucks and HBV in humans. (-)-beta-L-2',3'-Dideoxy-3'-thiacytidine (3TC; lamivudine) is a nucleoside analog which has demonstrated antiviral activity against HBV as well as human immunodeficiency virus (HIV). The purpose of the present investigation was to characterize the pharmacokinetics of 3TC following intravenous and oral administration of 20 mg of 3TC per kg of body weight to woodchucks. Following intravenous administration, the concentrations of 3TC in plasma declined, with a terminal half-life of 2.84 +/- 0.85 h (mean +/- standard deviation). The systemic clearance and steady-state volume of distribution of 3TC were 0.22 +/- 0.078 liters/h/kg and 0.75 +/- 0.13 liters/kg, respectively. The renal clearance of the nucleoside analog was 0.063 +/- 0.016 liters/h/kg. The oral bioavailability of 3TC ranged from 18 to 54%. Allometric relationships between pharmacokinetic parameters and body weight developed by Hussey et al. (E.K. Hussey, K.H. Donn, M.J. Daniel, S.T. Hall, A.J. Harker, and G.L. Evans, J. Clin. Pharmacol. 34:975-977, 1994) were augmented by including data from woodchucks, monkeys (S.M. Blaney, M.J. Daniel, A.J. Harker, K. Godwin, and F.M. Balis, Antimicrob. Agents Chemother. 39:2779-2782, 1995), and additional data from rats (P. Rajagopalan, L. Moore, C.K. Chu, R.F. Schinazi, and F.D. Boudinot, submitted for publication). Interspecies scaling of the pharmacokinetic parameters of 3TC demonstrated a good correlation between clearance (0.74 . W0.76 [where W is body weight]; r = 0.93; P < 0.025), apparent volume of distribution (1.62 . W0.81; r = 0.98; P < 0.005), and steady-state volume of distribution (1.09 . W0.94; r = 0.99; P < 0.05) and species body weight. The allometric relationships for clearance and volume of distribution at steady state predicted the observed pharmacokinetic parameters in humans quite well; however, the apparent volume of distribution was underestimated in humans. Thus, the pharmacokinetic data obtained with the woodchuck HBV animal model should be useful for designing clinical trials.
Adaptive Kalman Filter Control Law for Visual Servoing (2016)

We improve uncalibrated visual servoing for multiple cameras. This moves robots towards being more effective in unstructured environments. Our approach improves performance and reliability by prioritizing data from particular cameras in the system. Adaptive filtering is used to effect this in an uncalibrated situation. Rules are introduced for ensuring positive definite covariance estimates, with the resulting control law then compared to two prior methods. Performance metrics show that the new control law yields lower tracking error than previous approaches and the standard deviations of these metrics indicate that it provides a much more reliable system. Simulation results include improvements up to 33% in the performance metric for a static target and 63% in standard deviation of the performance metric for a moving target.
Role of Uteroglobin and Transglutaminase in Masking the Antigenicity of Implanting Rabbit Embryos* (1982)

Using rabbit as a model, the roles of uteroglobin (UG) and transglutaminase (TG) in masking the antigenicity of early developing mammalian embryo have been investigated. Maternal lymphocytes in vitro, when mixed with mitomycin-C inactivated blastomeres, incorporated H3-thymidine, suggesting recognition of embryonic antigens by these cells. However, pretreatment of blastomeres with pregnant uterine fluid (PUF) or with UG alone or in combination with TG (coagulation factor XIIIa), resulted in a significant and dose-dependent suppression of H3-thymidine incorporation into these lymphocytes. A complete suppression was achieved at a concentration of 250 micrograms of UG/ml, in the absence of TG. However, in the presence of TG, only 1.0 micrograms of UG/ml was required for total suppression. Neither nonpregnant uterine fluid (NPUF), nor myoglobin, a nonspecific protein similar in molecular weight to UG, had any suppressive effect. Incubation of uteroglobin with anti-UG or TG with its antiserum prior to the pretreatment of blastomeres eliminated the suppressive effect of these proteins. Inhibition of TG by neopentyl chloroethyl nitrosourea (NPCNU) also eliminated the suppressive effects of uteroglobin on H3-thymidine incorporation into maternal lymphocytes. These results suggest that in the pregnant uterus UG in conjunction with TG may play a specific role in masking the antigenicity of developing embryos during implantation.
Unusual Catalytic Triad of Escherichia coli Outer Membrane Phospholipase A (2000)

Escherichia coli outer membrane phospholipase A (OMPLA) is an integral membrane enzyme. OMPLA is active as a homodimer and requires calcium as a cofactor. The crystal structures of the monomeric and the inhibited dimeric enzymes were recently determined [Snijder, H. J., et al. (1999) Nature 401, 717-721] and revealed that OMPLA monomers are folded into a 12-stranded antiparallel beta-barrel. The active site consists of previously identified essential residues Ser144 and His142 in an arrangement resembling the corresponding residues of a serine hydrolase catalytic triad. However, instead of an Asp or Glu that normally is present in the triad of serine hydrolases, a neutral asparagine (Asn156) was found in OMPLA. In this paper, the importance of the catalytic Asn156 is addressed by site-directed mutagenesis studies. All variants were purified at a 30 mg scale, and were shown to be properly folded using SDS-PAGE and circular dichroism spectroscopy. Using chemical cross-linking, it was shown that all variants were not affected in their calcium-dependent dimerization properties. The Asn156Asp variant exhibited a 2-fold lower activity than wild-type OMPLA at neutral pH. Interestingly, the activity of the variant is 1 order of magnitude higher than that of the wild type at pH >10. Modest residual activities (5 and 2.5%, respectively) were obtained for the Asn156Ala and Asn156Gln mutants, showing that the active site of OMPLA is more tolerant toward replacements of this third residue of the catalytic triad than other serine hydrolases, and that the serine and histidine residues are minimally required for catalysis. In the X-ray structure of dimeric OMPLA, the cofactor calcium is coordinating the putative oxyanion via two water molecules. We propose that this may lessen the importance for the asparagine in the catalytic triad of OMPLA.
Enhanced empirical large-signal model for HBTs with performance comparable with physics-based models (2004)

An accurate empirical large-signal model for an heterojunction bipolar transistor (HBT) is given. In the DC mode, thermal-dependent physics-based relations for Kirk and avalanche effects are included to improve the accuracy of the model. In the small-signal mode, in addition to the distribution of the base resistance and base collector junction, the model captures the variation of various AC parameters with both bias voltage and bias current over the entire forward-bias region and a wide range of signal frequencies. DC parameter extraction is easily carried out using suitable optimisation codes on the measured Ic–Vce curves and Gummel plots, whereas the AC parameters are determined from multibias S-parameter measurements. To assess the validity and the accuracy of the proposed model the empirical large-signal model is constructed for a 2×25 μm2 emitter-area transistor and compared with measurements in DC, small-signal and large-signal modes. The model is further tested by comparing it with the physics-based and well-established VBIC model. It is found that, despite its reduced complexity, the enhanced empirical model gives better agreement with measurements than the VBIC model in all modes of operation.
Tidal effects on long‐range sound transmission (1981)

Time series of acoustic travel times over long distances have significant tidal components. We discuss three experiments: First, for a 900 km westward transmission from a moored source southwest of Bermuda, the M 2 constituent (apart from mooring motion) of 8 ms can be accounted for by a variable propagation with and against the 2 cm/s barotropic tidal current. The situation is different for the K 1 and S 2 constituents (which have a significant solar component), particularly for rays with shallow turning points, suggesting an effect from a minute daily variation in the temperature of the upper 100 m. Second, for a 500 km transmission from the Bahamas northward and parallel to the continental margin, the measured M 2 constituent is not in phase with the computed effect of the barotropic tidal current, unlike the westward transmission mentioned above. Here the mode conversion from barotropic to baroclinic tides plays a crucial role: the principal cause of the travel time oscillations in quadrature with the tidal current is a vertical oscillation by several meters (and attendant temperature and sound speed fluctuations) associated with the baroclinic tide just seaward of the continental margin, in the near‐zone of mode conversion. Third, for 300 km transmissions from a moored source northwest of Bermuda to both a moored receiver and a landbased receiver, the tidal components in the travel time are dominated by tidally induced mooring motions. The tidal amplitude varies in time as the tidal mooring motion is modulated by the variable current (because of the nonlinear drag), and the current can be so estimated. An important part, possibly a predominant part, of the (nontidal) travel time variation of 0.7 s is evidently associated with the mean mooring motion.—The interpretation of the tidal fluctuations in travel time is varied and complex.
Novel insights into construct toxicity, strain optimization, and primary sequence design for producing recombinant silk fibroin and elastin-like peptide in E. coli (2023)

Spider silk proteins (spidroins) are a remarkable class of biomaterials that exhibit a unique combination of high-value attributes and can be processed into numerous morphologies for targeted applications in diverse fields. Recombinant production of spidroins represents the most promising route towards establishing the industrial production of the material, however, recombinant spider silk production suffers from fundamental difficulties that includes low titers, plasmid instability, and translational inefficiencies. In this work, we sought to gain a deeper understanding of upstream bottlenecks that exist in the field through the production of a panel of systematically varied spidroin sequences in multiple <i>E. coli</i> strains. A restriction on basal expression and specific genetic mutations related to stress responses were identified as primary factors that facilitated higher titers of the recombinant silk constructs. Using these findings, a novel strain of <i>E. coli</i> was created that produces recombinant silk constructs at levels 4-33 times higher than standard BL21(DE3). However, these findings did not extend to a similar recombinant protein, an elastin-like peptide. It was found that the recombinant silk proteins, but not the elastin-like peptide, exert toxicity on the <i>E. coli</i> host system, possibly through their high degree of intrinsic disorder. Along with strain engineering, a bioprocess design that utilizes longer culturing times and attenuated induction was found to raise recombinant silk titers by seven-fold and mitigate toxicity. Targeted alteration to the primary sequence of the recombinant silk constructs was also found to mitigate toxicity. These findings identify multiple points of focus for future work seeking to further optimize the recombinant production of silk proteins and is the first work to identify the intrinsic disorder and subsequent toxicity of certain spidroin constructs as a primary factor related to the difficulties of production.
Repositioning the salient region of videos by using active illumination (2015)

The use of networked light bulbs is proposed in order to modify the focus of attention, defined based on salience maps, of a video being displayed on a screen. The proposed system was evaluated by using four networked lamps positioned behind a television display. The lamps were controlled by the system according to the visual features of the video. By using a camera, the salience of the room illuminated by the smart bulbs was recorded and compared against the salience of the room when the lamps were not used. The results showed that changes in color and intensity of the environmental illumination were able to modify the shape of the salience maps of the displayed videos. Two modes of operation are proposed: salience cancellation and salience enhancement.
Coca-Cola, by near-ambient pressure XPS (2019)

Near ambient pressure-x-ray photoelectron spectroscopy (NAP-XPS) is a less traditional form of XPS that allows samples to be analyzed at relatively high pressures, i.e., at ca. 2500 Pa, or higher in some cases. With NAP-XPS, XPS can probe moderately volatile liquids, biological samples, porous materials, and/or polymeric materials that outgas significantly. In this submission, we show an NAP-XPS survey spectrum, and also O 1s and C 1s narrow scans, of a commercial soft drink, Coca-Cola. Clearly this is a material that could not be analyzed at moderate pressures by conventional XPS. The C 1s narrow scan is fit to five synthetic components. The O 1s narrow scan shows strong contributions from both liquid and gas phase water. A small N 1s signal in the survey spectrum is attributed to background nitrogen. The shape of the uniqueness plot corresponding to the C 1s fit suggests that the fit parameters are statistically significant.
Structurally Distinct Recognition Motifs in Lymphotoxin-β Receptor and CD40 for Tumor Necrosis Factor Receptor-associated Factor (TRAF)-mediated Signaling (2003)

Lymphotoxin-beta receptor (LTbetaR) and CD40 are members of the tumor necrosis factor family of signaling receptors that regulate cell survival or death through activation of NF-kappaB. These receptors transmit signals through downstream adaptor proteins called tumor necrosis factor receptor-associated factors (TRAFs). In this study, the crystal structure of a region of the cytoplasmic domain of LTbetaR bound to TRAF3 has revealed an unexpected new recognition motif, 388IPEEGD393, for TRAF3 binding. Although this motif is distinct in sequence and structure from the PVQET motif in CD40 and PIQCT in the regulator TRAF-associated NF-kappaB activator (TANK), recognition is mediated in the same binding crevice on the surface of TRAF3. The results reveal structurally adaptive "hot spots" in the TRAF3-binding crevice that promote molecular interactions driving specific signaling after contact with LTbetaR, CD40, or the downstream regulator TANK.
Uplink Downlink Rate Balancing and Throughput Scaling in FDD Massive MIMO Systems (2016)

In this work we extend the concept of uplink-downlink rate balancing to frequency division duplex (FDD) massive MIMO systems. In uplink-downlink balancing, we use part of the uplink capacity for CSI feedback in order to increase the downlink capacity. We consider a base station with large number antennas serving many single antenna users. We first show that any unused capacity in the uplink can be traded off for higher throughput in the downlink in a system that uses either dirty paper (DP) coding or zero-forcing (ZF) precoding. We then also study the scaling of the system throughput with the number of antennas in cases of Beamforming (BF) Precoding, ZF Precoding, and DP coding. We show that the downlink throughput is proportional to the logarithm of the number of antennas. While, this logarithmic scaling is lower than the linear scaling of the rate in the uplink, it can still bring significant throughput gains. For example, we demonstrate through analysis and simulation that increasing the number of antennas from 4 to 128 will increase the throughput by more than a factor of 5. We also show that a logarithmic scaling of downlink throughput as a function of the number of receive antennas can be achieved even when the number of transmit antennas only increases logarithmically with the number of receive antennas.
Preface: phys. stat. sol. (c) 5/6 (2008)

Abstract The 7th International Conference of Nitride Semiconductors (ICNS‐7) was held at the MGM Grand Hotel in Las Vegas, Nevada, USA, from 16–21 September 2007. A record number of more than 900 registered participants gathered in Las Vegas to hear the most recent developments in nitride semiconductors. A total of 694 papers, divided into more than 40 sessions, were presented at the conference covering every aspect of group‐III nitride semiconductor research. The title of the Plenary Talk given by Prof. Klaus H. Ploog, “ III‐Nitrides Seem to Be Good for Everything, ” was indeed accurate. The present issue of physica status solidi contains more than 300 peer‐reviewed scientific papers describing the state‐of‐the‐art in nitride semiconductor materials and devices, as presented at ICNS‐7. The diligent work of the many authors and referees involved in these proceedings (more than 400) has been fundamental for the successful completion of this important record of the conference. Finally, the conference organizers would also like to acknowledge and thank the many sponsors and public agencies that have financially supported ICNS‐7. Without their help, ICNS‐7 would have never become the largest nitride conference ever. Thank you also to all the participants who, with their papers and discussions, have made ICNS‐7 a tremendous success. We look forward to new exciting developments in nitride semiconductors at ICNS‐8 in Jeju Island, Korea, in October 2009. (© 2008 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
A wideband axially symmetric antenna design fabricated with additive and subtractive methods (2016)

An antenna design technique that makes use of axial symmetry to realize efficient wideband or multiband operation is presented. The antenna is created by optimizing a two-dimensional profile using a global optimization strategy such as the Covariance Matrix Adaptation Evolutionary Strategy (CMA-ES) and sweeping the curve around an axis to form a solid body of revolution. A method-of-moments simulation tool is used to characterize the candidate antenna solutions according to the user-defined cost function. An ultra-wideband example antenna is optimized here to illustrate the design capability. The design is fabricated using 3D printing and lathe-based manufacturing methods and tested to verify predicted performance.
A Numerical and Experimental Analysis of Cardiovascular Stent Design Considerations (2003)

Stents have proven very effective in opening the lumens of blocked and diseased arteries, leading to an increased quality of life for thousand of patients. Due to their success, stents have grown into a $1.5 billion dollar industry, but unfortunately still suffer from failure rates of 20–30% in the first year. Many of these failures can be traced back to restenosis or thrombosis of the stented arteries, a problem which conventional self-expanding or balloon-expanded stents have not proved effective in combating. Mathematical and experimental research shows that stents create adverse flow conditions and increase the stresses found around the implants, and trials of designs intended to reduce these effects have proven effective in combating restenosis. The goal of this research was to investigate mathematically design considerations for an improved stent that can reduce these negative effects. This was accomplished through the construction of a onedimensional numerical model for the fluid mechanics of the artery that was implemented using FEA and a combination of WENO and Runge-Kutta methods. The output from this model was compared with solutions from the literature and with in-vitro experimental results. Based on these tests it was concluded that the model accurately predicted the behavior of the pressure waves in a vessel. These numerical models were then used to evaluate several proposed designs. The pressure wave reflection was found to be controlled entirely by the design of the stent ends; mid-length variations in stent compliance provided no change in the model behavior. Also, a region of gradual transition between the low stiffness of the artery and the increased stiffness of the stent, while useful for reducing wall stresses, proved ineffective in reducing the magnitude of the reflected pressure waves. The best design for minimizing pressure wave reflection was found to be one that minimized total stent length.
Data from Detection of Gastric Cancer with Novel Methylated DNA Markers: Discovery, Tissue Validation, and Pilot Testing in Plasma (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Gastric adenocarcinoma is the third most common cause of cancer mortality worldwide. Accurate and affordable noninvasive detection methods have potential value for screening and surveillance. Herein, we identify novel methylated DNA markers (MDM) for gastric adenocarcinoma, validate their discrimination for gastric adenocarcinoma in tissues from geographically separate cohorts, explore marker acquisition through the oncogenic cascade, and describe distributions of candidate MDMs in plasma from gastric adenocarcinoma cases and normal controls.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; Following discovery by unbiased whole-methylome sequencing, candidate MDMs were validated by blinded methylation-specific PCR in archival case–control tissues from U.S. and South Korean patients. Top MDMs were then assayed by an analytically sensitive method (quantitative real-time allele-specific target and signal amplification) in a blinded pilot study on archival plasma from gastric adenocarcinoma cases and normal controls.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Whole-methylome discovery yielded novel and highly discriminant candidate MDMs. In tissue, a panel of candidate MDMs detected gastric adenocarcinoma in 92% to 100% of U.S. and South Korean cohorts at 100% specificity. Levels of most MDMs increased progressively from normal mucosa through metaplasia, adenoma, and gastric adenocarcinoma with variation in points of greatest marker acquisition. In plasma, a 3-marker panel (&lt;i&gt;ELMO1, ZNF569, C13orf18)&lt;/i&gt; detected 86% (95% CI, 71–95) of gastric adenocarcinomas at 95% specificity.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Novel MDMs appear to accurately discriminate gastric adenocarcinoma from normal controls in both tissue and plasma. The point of aberrant methylation during oncogenesis varies by MDM, which may have relevance to marker selection in clinical applications. Further exploration of these MDMs for gastric adenocarcinoma screening and surveillance is warranted. &lt;i&gt;Clin Cancer Res; 24(22); 5724–34. ©2018 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;