gebhart/patrepeval huggingface dataset:
Regulation of acetylcholine receptor alpha subunit variants in human myasthenia gravis. Quantification of steady-state levels of messenger RNA in muscle biopsy using the polymerase chain reaction. (1994)

Myasthenia gravis (MG) is an autoimmune disease mediated by auto-antibodies that attack the nicotinic acetylcholine receptor (AChR). To elucidate the molecular mechanisms underlying the decrease in AChR levels at the neuromuscular junction, we investigated the regulation of AChR expression by analyzing mRNA of the two AChR alpha subunit isoforms (P3A+ and P3A-) in muscle samples from myasthenic patients relative to controls. We applied a quantitative method based on reverse transcription of total RNA followed by polymerase chain reaction (PCR), using an internal standard we constructed by site-directed mutagenesis. An increased expression of mRNA coding for the alpha subunit of the AChR isoforms was observed in severely affected patients (P < 0.003 versus controls) but not in moderately affected patients, independently of the anti-AChR antibody titer. Study of mRNA precursor levels indicates a higher expression in severely affected patients compared to controls, suggesting an enhanced rate of transcription of the message coding for the alpha subunit isoforms in these patients. We have also reported that mRNA encoding both isoforms are expressed at an approximate 1:1 ratio in controls and in patients. We have thus identified a new biological parameter correlated with disease severity, and provide evidence of a compensatory mechanism to balance the loss of AChR in human myasthenia gravis, which is probably triggered only above a certain degree of AChR loss.
The nanocoherer: an electrically and mechanically resettable resistive switching device based on gold clusters assembled on paper (2018)

We report the realization of a resettable resistive switching device based on a nanostructured film fabricated by supersonic cluster beam deposition of gold clusters on plain paper substrates. Through the application of suitable voltage ramps, we obtain, in the same device, either a complex pattern of resistive switchings, or reproducible and stable switchings between low resistance and high resistance states, with an amplitude up to five orders of magnitude. Our device retains a state of internal resistance following the history of the applied voltage similar to that reported for memristors. The two different switching regimes in the same device are both stable, the transition between them is reversible, and it can be controlled by applying voltage ramps or by mechanical deformation of the substrate. The device behavior can be related to the formation, growth and breaking of junctions between the loosely aggregated gold clusters forming the nanostructured films. The fact that our cluster-assembled device is mechanically resettable suggests that it can be considered as the analog of the coherer: a switching device based on metallic powders used for the first radio communication system.
Inhibitory effects of selected antiviral compounds on human hepatitis B virus DNA synthesis (1991)

By using an assay system based on a human hepatoblastoma cell line (HB611) that continuously synthesizes hepatitis B virus DNA, the following compounds were found to inhibit hepatitis B virus DNA synthesis at concentrations that were significantly lower than their minimum cytotoxic concentrations: 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine, 9-(phosphonylmethoxyethyl)adenine, 2',3'-dideoxy-2',3'-didehydrocytidine, and 2',3'-dideoxycytidine. The most potent compound was PMEDAP (50% effective concentration, 0.02 micrograms/ml). The selective index, or ratio of the 50% cytotoxic concentration to 50% effective concentration, of PMEDAP was greater than 750.
Rpn4 Is a Physiological Substrate of the Ubr2 Ubiquitin Ligase (2004)

The homeostatic abundance of the proteasome in Saccharomyces cerevisiae is controlled by a feedback circuit in which transcriptional activator Rpn4 up-regulates the proteasome genes and is destroyed by the assembled, active proteasome. Remarkably, the degradation of Rpn4 can be mediated by two independent pathways. One pathway is independent of ubiquitin, whereas the other involves ubiquitination on internal lysines. In the present study, we investigated the mechanism underlying the ubiquitin-dependent degradation of Rpn4. We demonstrated, through in vivo and in vitro assays, that Rpn4 is a physiological substrate of the Ubr2 ubiquitin ligase, which was originally identified as a sequence homolog of Ubr1, the E3 component of the N-end rule pathway. The ubiquitin-conjugating enzyme Rad6, which directly interacts with Ubr2, is also required for the ubiquitin-dependent degradation of Rpn4. Furthermore, we showed that deletion of UBR2 exhibited a strong synthetic growth defect with a mutation in the Rpt1 proteasome subunit when Rpn4 was overexpressed. This study not only identified the ubiquitination apparatus for Rpn4 but also unveiled the first physiological substrate of Ubr2. The biological significance of Ubr2-mediated degradation of Rpn4 is also discussed.
Clinical pharmacology of the stereoisomers of leucovorin during repeated oral dosing (1989)

As part of a clinical trial of cisplatin, 5-fluorouracil (5-FU), and leucovorin (LV) for treatment of patients with advanced head and neck cancer, patients received 100 mg of LV (d,l-5-formyltetrahydrofolate) orally every 4 hours for 5 days. On days 2 and 4 of treatment, plasma samples were obtained 2 hours after (peak) and 30 minutes before (trough) a dose of LV. Total LV and 5-methyltetrahydrofolate (THF) concentrations were measured with high-performance liquid chromatography (HPLC) analysis. LV stereoisomer concentrations were determined by chiral HPLC on a bovine serum albumin-bonded silica column. Thus far, plasma folate levels have been analyzed for ten cycles of treatment administered to 7 patients (40 samples). Administration of LV in divided oral doses approximates a plasma steady state with no significant differences noted between peak and trough concentrations. Mean (+/- SD) plasma concentrations for all samples were (mumol): LV, 3.2 +/- 1.3; l-LV, 0.28 +/- 0.21; d-LV, 2.9 +/- 1.2; and THF, 4.25 +/- 2.5. Plasma levels of d-LV and THF tended to be approximately 10% higher on day 4 than day 2, although mean differences were not significantly different due to substantial interpatient variability. Of note was that the sum of THF and l-LV exceeds that of d-LV which was consistent with selective absorption of the l-isomer of LV. Mean ratios of d-LV/l-LV and d-LV/l-LV and THF were 13.7 +/- 10 and 0.88 +/- 0.68, respectively. The authors conclude that oral administration of LV in divided dose (1) simulates a continuous intravenous infusion; (2) produces plasma levels of l-reduced folates in a range known to potentiate 5-FU cytotoxicity; and (3) results in low ratios of d/l-reduced folates that may be important in maximizing the effectiveness of 5-FU-LV chemotherapy.
Microresonator-based comb generation without an external laser source (2014)

We demonstrate a fiber-microresonator dual-cavity architecture with which we generate 880 nm of comb bandwidth without the need for a continuous-wave pump laser. Comb generation with this pumping scheme is greatly simplified as compared to pumping with a single frequency laser, and the generated combs are inherently robust due to the intrinsic feedback mechanism. Temporal and radio frequency (RF) characterization show a regime of steady comb formation that operates with reduced RF amplitude noise. The dual-cavity design is capable of being integrated on-chip and offers the potential of a turn-key broadband multiple wavelength source.
Using Social Group Trajectories for Potential Impersonation Detection on Smart Buildings Access Control (2019)

In many domains, applications use people trajectories' spatiotemporal data for impersonation fraud detection purposes. Anomaly-based approaches consist in constructing mobility profiles based on users' frequent paths and schedules and comparing new trajectories against these profiles: if some new trajectory is not consistent with the user profile, a potential impersonation is detected. Previous studies, however, do not include traveling companions in users' profiles, although performing activities in social groups is inherent to human behavior. Physical access control systems on smart buildings can provide activity companions information since social groups naturally emerge on organizations hosted in such buildings and these systems can capture group trajectories. This paper explores the feasibility of using spatiotemporal mobility profiles enriched with group trajectory pattern data as a novel framework for impersonation fraud detection in smart buildings. An empirical analysis is conducted, and results show that it is feasible to add companions activities information to mobility profiles in order to enhance anomaly-based impersonation attack detection.
Multi-Level Halftoning by IGS Quantization (2013)

Improved gray-scale (IGS) quantization is a known method for re-quantizing digital gray-scale images for data compression while producing halftones by adding a level of randomness to improve visual quality of the resultant images. In this paper, first, analyzing the IGS quantizing operations reveals the capability of conserving a DC signal level of a source image through the quantization. Then, a complete procedure for producing a multi-level halftone image by IGS quantization that can achieve the DC conservation is presented. Also, the procedure uses the scanning of source pixels in an order such that geometric patterns can be prevented from occurring in the resulting halftone image. Next, the performance of the multi-level IGS halftoning is evaluated by experiments conducted on 8-bit gray-scale test images in comparison with the halftoning by error diffusion. The experimental result demonstrates that a signal level to be quantized in the IGS halftoning varies more randomly than that in the error diffusion halftoning, but not entirely randomly. Also, visual quality of the resulting halftone images was measured by subjective evaluations of viewers. The result indicates that for 3 or more-bit, in other words, 8 or more-level halftones, the IGS halftoning achieves image quality comparable to that by the error diffusion.
Time-resolved study of phonon polaritons in<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline"><mml:mrow><mml:msub><mml:mrow><mml:mi mathvariant="normal">LiTaO</mml:mi></mml:mrow><mml:mrow><mml:mn>3</mml:mn></mml:mrow></mml:msub></mml:mrow></mml:math> (1993)

We study the temperature dependence of the low-frequency dielectric properties of the ferroelectric ${\mathrm{LiTaO}}_{3}$ by generating phonon polaritons with frequencies in the terahertz regime. The phonon polaritons are impulsively excited and phase-sensitively detected with 60-fs laser pulses. The propagation and damping of the polaritons are investigated as a function of frequency and temperature. The experimental results are compared with a quantum-mechanical model for the low-frequency dielectric response of ${\mathrm{LiTaO}}_{3}$. In this model the lowest-energy ${\mathit{A}}_{1}$ mode is described with a one-dimensional anharmonic potential in a single unit cell. We find that at 300 K the polariton dispersion and damping are determined by a strong resonance at 6 THz and a weak resonance at 1 THz. The latter resonance is due to a tunneling transition and leads to the observation of phonon-polariton beats. The model predicts that with increasing temperature the strength of the resonance at 6 THz decreases and that a new broad resonance at 3 THz and a central mode arise. The measured polariton dispersion and damping are in quantitative agreement with these theoretical predictions. Thereby we obtain evidence that the ferroelectric phase transition in ${\mathrm{LiTaO}}_{3}$ takes place without mode softening.
Allelic deletions of the VHL gene detected in multiple microscopic clear cell renal lesions in von Hippel-Lindau disease patients. (1996)

Patients with von Hippel-Lindau (VHL) disease develop a spectrum of bilateral clear-cell renal lesions including cysts and renal cell carcinomas (RCCs). VHL gene deletions have been previously reported in VHL-associated macroscopic RCC. Although histological analysis suggests that microscopic cystic lesions in the VHL patients may represent precursors of the RCC, there is at present no direct molecular evidence of their relationship. To investigate the relationship between cystic lesions and RCC, 26 microdissected archival renal lesions from two VHL disease patients were studied for loss of heterozygosity at the VHL gene locus using polymerase chain reaction single-strand conformation polymorphism analysis. The renal lesions included 2 benign cysts, 5 atypical cysts, 5 microscopic RCCs in situ, 5 cysts lined by a single layer of cells, in which RCCs in situ were developing, and 2 microscopic and 7 macroscopic RCCs. Except for a single benign cyst, 25 of 26 renal lesions showed nonrandom allelic loss of the VHL gene. In either of the 2 patients, the same VHL allele was deleted in all of the lesions tested, indicating loss of the wild-type allele and retention of the inherited, mutated VHL allele. The results suggest that all clear-cell lesions in the VHL kidney represent neoplasms and that the loss of the VHL gene occurs early in their development. Atypical and benign cysts most likely represent the initial phenotype in malignant transformation to the RCC.
A perturbation approach for optical diffusion tomography using continuous-wave and time-resolved data (1993)

In this paper, we discuss approaches our group has developed for the problem of imaging the interior of dense scattering media [1]. While our principal focus is on potential biomedical applications, we believe our methods are sufficiently general to have applications to other imaging problems as well. We begin our consideration of the imaging problem by assuming that the target medium of interest interacts with the penetrating energy source with sufficient strength to cause intense scattering. We further assume that for essentially all practical schemes, only the multiply scat- tered signal is measurable. One result of multiple scattering is that all the detected photons will have propagated above and below the plane in which the source and de- tector lie. Thus, it becomes necessary to explicitly consider volume functions whose spatial distribution will depend on the properties and geometry of the medium and on the geometry and type of illumination scheme. Measurement schemes which have been suggested include steady-state [2], ultrafast [3-5], and amplitude mod- ulated [6, 7] sources. Other schemes include holographic methods which have the potential advantages of directly yielding an image without the need for numerical reconstruction [8, 9]. In developing approaches to image reconstruction, our group has emphasized the first two of the four methods [10-16].
Insulin inhibits pertussis toxin-catalyzed ADP-ribosylation of G-proteins. Evidence for a novel interaction between insulin receptors and G-proteins. (1988)

Insulin modifies cellular responsiveness to some hormones which operate via guanine nucleotide binding proteins (G-proteins); also, G-proteins have been implicated in some actions of insulin. Using pertussis toxin-catalyzed [32P]ADP-ribosylation of Gi as an index of G-protein conformation, we evaluated interaction of insulin receptors with G-proteins. In isolated rat liver plasma membranes, insulin treatment for 10 min inhibited [32P]ADP-ribosylation of Gi by 50%. This effect was half-maximal at 2 x 10(-8) M. A similar effect was observed with rat adipocyte plasma membranes with half-maximal effect at 1 x 10(-8) M. Pertussis toxin activity itself was uninfluenced by insulin, as ribosylation of tubulin or heat-treated bovine serum albumin was unaltered. Elevated Mg2+ diminished basal ADP-ribosylation, but insulin inhibition occurred at all Mg2+ levels between 0 and 1 mM. Insulin inhibition was independent of ATP (20 microM to 10 mM), and GTP (0-100 microM) concentrations. Because both protein kinase C and purified insulin receptor phosphorylate purified Gi in vitro, we examined Gi as a substrate for the insulin receptor tyrosine kinase in vivo. Triton-extracts of isolated rat hepatocytes which had been 32Pi labeled and treated with insulin were immunoprecipitated with a polyclonal anti-Gi antiserum. The dominant labeled phosphoprotein had a molecular weight of 42 kDa, consistent with the alpha-subunit of Gi, contained only phosphoserine, and was unaffected in its phosphorylation by insulin. These results indicate the existence of a novel pathway for physiological "cross-talk" between insulin and other hormones and further suggests that the insulin receptor may interact with regulatory G-proteins via biochemical mechanisms not directly involving the tyrosine kinase activity of the insulin receptor.
Cerebral [<sup>15</sup>O]Water Clearance in Humans Determined by PET: I. Theory and Normal Values (1996)

When used to measure blood flow in the brain, water leaves a residue in the vascular bed that influences the estimation of blood flow by current methods. To assess the magnitude of this influence, we developed a two-compartment model of blood flow with separate parameters for transport and vascular distribution of brain water. Maps of the water clearance, K1 into brain tissue, separated from the circulation by a measurably resistant blood-brain barrier (BBB), were generated by time-weighted integration. Depending on the validity of the assumptions underlying the two-compartment model presented here, the maps revealed a significant overestimation of the clearance of water when the vascular residue was ignored. Maps of Vo, the estimate of the apparent vascular distribution volume of tracer H2(15)O, clearly revealed major cerebral arteries. Thus, we claim that the accumulation of radioactive water in brain tissue also reflects the volume of the arterial vascular bed of the brain.
Robust PCA for Anomaly Detection in Cyber Networks (2018)

This paper uses network packet capture data to demonstrate how Robust Principal Component Analysis (RPCA) can be used in a new way to detect anomalies which serve as cyber-network attack indicators. The approach requires only a few parameters to be learned using partitioned training data and shows promise of ameliorating the need for an exhaustive set of examples of different types of network attacks. For Lincoln Lab's DARPA intrusion detection data set, the method achieves low false-positive rates while maintaining reasonable true-positive rates on individual packets. In addition, the method correctly detected packet streams in which an attack which was not previously encountered, or trained on, appears.
MUC1* Mediates the Growth of Human Pluripotent Stem Cells (2008)

The MUC1 protein is aberrantly expressed on an estimated 75% of all human solid tumor cancers. We recently reported that a transmembrane cleavage product, MUC1*, is the predominant form of the protein on cancer cells [1]. Further, our evidence indicated that MUC1* functions as a growth factor receptor on tumor cells, while the full-length protein appeared to have no growth promoting activity. Here, we report that MUC1* acts as a growth factor receptor on undifferentiated human embryonic stem cells (hESCs). Cleavage of the full-length ectodomain to form MUC1*, a membrane receptor, appears to make binding to its ligand, NM23, possible. Unexpectedly, we found that newly differentiated cells no longer express the cleaved form, MUC1*, or its ligand, NM23. Newly differentiated stem cells exclusively present full-length MUC1. Antibody-induced dimerization of the MUC1* receptor on hESCs stimulated cell growth to a far greater degree than currently used methods that require the addition of exogenous basic fibroblast growth factor (bFGF) as well as factors secreted by fibroblast "feeder cells". Further, MUC1* mediated growth was shown to be independent of growth stimulated by bFGF or the milieu of factors secreted by feeder cells. Stimulating the MUC1* receptor with either the cognate antibody or its ligand NM23 enabled hESC growth in a feeder cell-free system and produced pluripotent colonies that resisted spontaneous differentiation. These findings suggest that this primal growth mechanism could be utilized to propagate large numbers of pluripotent stem cells for therapeutic interventions.
Effects of knee position on blood loss following total knee arthroplasty: a randomized, controlled study (2015)

Blood loss following total knee arthroplasty is a serious side-effect of surgery and impacts on patient recovery and quality of life. The aim of this study was to assess the effect of postoperative knee position during recovery on blood loss and range of motion. One hundred consecutive patients, with stage III or IV degenerative osteoarthritis, were enrolled in the study and randomized equally between two treatment groups: flexion and extension. In the flexion group, the affected leg was elevated postoperatively by 45° at the hip, with 45° flexion at the knee, while patients in the extension group had the knee extended fully. Blood loss, pre- and postoperative hemoglobin levels, and range of motion were recorded together with duration of hospital stay and complications. Calculated blood loss, hidden blood loss, and postoperative hemoglobin levels between the two groups were significantly different, with patients in the flexion group experiencing lower blood loss than those in the extension group (P < 0.05). After 6-week rehabilitation, patients from both groups attained a similar range of motion in the joint. Duration of hospital stay was shorter in the flexion group by 1.6 days. Wound infection rates were similar in both groups, and we observed no proven deep vein thrombosis. Postoperative elevation of the hip by 45°, with 45° knee flexion, is an effective and simple method of reducing blood loss and hospital stay following unilateral primary total knee arthroplasty.
Infectious Middle East Respiratory Syndrome Coronavirus Excretion and Serotype Variability Based on Live Virus Isolates from Patients in Saudi Arabia (2015)

The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 1,082 people, including 439 fatalities. So far, no empirical virus isolation study has been done to elucidate infectious virus secretion or serotype variability. Here, we used 51 respiratory samples from 32 patients with confirmed MERS-CoV infection for virus isolation in Vero B4 and Caco-2 cells. We found Caco-2 cells to significantly enhance isolation success over routinely used Vero cells. Isolation success correlated with viral RNA concentration and time after diagnosis as well as with the amount of IgA antibodies secreted in respiratory samples used for isolation. Results from plaque reduction neutralization assays using a representative range of serum samples and virus isolates suggested that all circulating human MERS-CoV strains represent one single serotype. The choice of prototype strain is not likely to influence the success of candidate MERS-CoV vaccines. However, vaccine formulations should be evaluated for their potential to induce IgA.
Reaction of <i>N,N'</i>‐dialkyldithiodianilines with β‐ketoesters. A new synthesis of <i>N</i>‐alkyl‐2‐acyl‐3‐oxo‐3,4‐dihydro‐1,4‐benzothiazines (1992)

Abstract The title compounds 3a‐j together with the N ‐alkylacylketene S,N ‐acetals 12a‐j were obtained by reaction of N,N' ‐dialkyldithiodianilines with β‐ketoesters compounds. A possible reaction pathway is suggested.