gebhart/patrepeval huggingface dataset:
Vasoactivity of Rucaparib, a PARP-1 Inhibitor, is a Complex Process that Involves Myosin Light Chain Kinase, P2 Receptors, and PARP Itself (2015)

Therapeutic inhibition of poly(ADP-ribose) polymerase (PARP), as monotherapy or to supplement the potencies of other agents, is a promising strategy in cancer treatment. We previously reported that the first PARP inhibitor to enter clinical trial, rucaparib (AG014699), induced vasodilation in vivo in xenografts, potentiating response to temozolomide. We now report that rucaparib inhibits the activity of the muscle contraction mediator myosin light chain kinase (MLCK) 10-fold more potently than its commercially available inhibitor ML-9. Moreover, rucaparib produces additive relaxation above the maximal degree achievable with ML-9, suggesting that MLCK inhibition is not solely responsible for dilation. Inhibition of nitric oxide synthesis using L-NMMA also failed to impact rucaparib's activity. Rucaparib contains the nicotinamide pharmacophore, suggesting it may inhibit other NAD+-dependent processes. NAD+ exerts P2 purinergic receptor-dependent inhibition of smooth muscle contraction. Indiscriminate blockade of the P2 purinergic receptors with suramin abrogated rucaparib-induced vasodilation in rat arterial tissue without affecting ML-9-evoked dilation, although the specific receptor subtypes responsible have not been unequivocally identified. Furthermore, dorsal window chamber and real time tumor vessel perfusion analyses in PARP-1-/- mice indicate a potential role for PARP in dilation of tumor-recruited vessels. Finally, rucaparib provoked relaxation in 70% of patient-derived tumor-associated vessels. These data provide tantalising evidence of the complexity of the mechanism underlying rucaparib-mediated vasodilation.
Room temperature single electron effects in a Si nano-crystal memory (1999)

An MOS memory based on Si nano-crystals has been fabricated. We have developed a repeatable process of forming uniform, small-size and high-density Si nano-crystals and spherical nano-crystals of about 4.5 nm in diameter with density of 5/spl times/10/sup 11//cm/sup 2/ were obtained. Threshold voltage shift of 0.48 V corresponding to single electron storage in individual nano-crystals is obtained. For the first time, room temperature single electron effects are observed. These prove the feasibility of practical Si nano-crystal memory.
Liposomal doxorubicin circumvents PSC 833-free drug interactions, resulting in effective therapy of multidrug-resistant solid tumors. (1997)

Conventional methods that are used to overcome multidrug resistance (MDR) often involve the coadministration of chemosensitizers and anticancer drugs. The cyclosporin analogue SDZ PSC 833 [(3'-keto-Bmt1)-(Val2)-cyclosporin] (PSC 833) has been shown to possess powerful chemosensitization properties in vitro, in addition to being intrinsically nontoxic. However, coadministration of PSC 833 with anticancer drugs, such as daunorubicin, doxorubicin (DOX), and Taxol, have resulted in the exacerbation of anticancer drug toxicity, which is due to altered anticancer drug pharmacokinetics. Here, we hypothesized that optimization of the anticancer drug delivery, using liposomal carriers, may, by avoiding these adverse interactions, offer a significant advantage over nonencapsulated drugs. Toxicity studies were conducted in normal BDF1 mice, with i.v. DOX (free or liposome encapsulated) administration and p.o. PSC 833 in single and multiple dosage regimens over a 15-day study period. p.o. administration of PSC 833, at a dose of 100 mg/kg, reduced the maximum tolerated dose (MTD) of i.v administered free drug by 2.5-3-fold, in single- and multiple-dose regimens. In contrast, PSC 833 administration resulted in only a 20% reduction of the MTD for DOX encapsulated in 100-nm 1,2 distearoyl-sn-glycero-3-phosphocholine/cholesterol liposomes (55:45 molar lipid ratio) in a single-dose regimen and had no effect on the liposomal DOX MTD for the day 1, 5, and 9 treatment schedule. Modest modulation of P-glycoprotein-mediated MDR was observed in the murine P388/ADR solid tumor model when PSC 833 was administered with free DOX at the MTD. In contrast, liposomal DOX combined with PSC 833 resulted in tumor growth inhibition that was comparable to that observed for drug-sensitive P388/WT tumors. This efficacy of P388/ADR tumors treatment was dependent on PSC 833 because treatment with liposomal DOX alone provided significantly less antitumor activity. Pharmacokinetic and tissue distribution data demonstrated that DOX encapsulated in 1,2 distearoyl-sn-glycero-3-phosphocholine/cholesterol liposomes exhibited comparable plasma elimination and tissue distribution properties in the presence and absence of PSC 833, whereas free DOX displayed reduced plasma elimination rates and altered tissue distribution in the presence of PSC 833. These results provide evidence that PSC 833 can induce P-glycoprotein modulation and chemosensitize MDR tumors in the absence of altered DOX pharmacokinetics when liposomal carriers are used. This suggests that the improved tumor selectivity of anticancer drugs that are administered in liposomal formulations may avoid the complications that are associated with free drug-MDR-reversing agent combinations and enhance the therapy of multidrug-resistant tumors.
Fiber optic sensors for predictive health monitoring (2002)

The ability to predict the onset of failure in mechanical systems is key to the reduction in maintenance costs, downtime, and health hazards in industrial environments. Vibration monitoring can be used to spot mechanical problems, trigger preventative maintenance and diagnose the health of rotating machinery. A variety of MEMS accelerometers and piezoelectric acoustic emission sensors are used in health monitoring that are limited by their size, cost, and performance. Optical fiber sensors are rapidly emerging as viable alternatives to these devices as effective means of health monitoring in harsh environments. These sensors are tolerant to extreme temperature, EMI, shock and vibration, and offer reduced weight and increased accuracy over conventional instrumentation. As a result, these sensors have begun to replace conventional sensors in harsh environment applications. Optical fiber sensors offer much smaller size, reduced weight, ability to operate at temperatures up to 2000/spl deg/C, immunity to electromagnetic interference, resistance to corrosive environments, inherent safety within flammable environments, and the ability to multiplex multiple sensors on a single optical fiber. This paper presents the research and development of both low-profile fiber optic-based acoustic emissions sensors for use in nondestructive evaluation systems and fiber optic accelerometers for harsh environment health monitoring applications.
Extended Baum transformations for general functions (2004)

The discrimination technique for estimating the parameters of Gaussian mixtures that is based on the extended Baum transformations (EB) has had significant impact on the speech recognition community. There appear to be no published proofs that definitively show that these transformations increase the value of an objective function with iteration (i.e., so-called "growth transformations"). The proof presented in the current paper is based on the linearization process and the explicit growth estimate for linear forms of Gaussian mixtures. We also derive new transformation formulae for estimating the parameters of Gaussian mixtures generalizing the EB algorithm, and run simulation experiments comparing different growth transformations.
FTY720 Pharmacokinetics in Mild to Moderate Hepatic Impairment (2005)

The influence of mild and moderate hepatic impairment on FTY720 pharmacokinetics was assessed. The authors enrolled 32 subjects consisting of 8 with mild and 8 with moderate hepatic impairment based on Child-Pugh criteria and 16 demographically matched control subjects. A single 1-mg oral dose of FTY720 was administered under fasting conditions. Blood, plasma, and urine samples were obtained over a 14-day period for measurement of FTY720 and metabolite concentrations and protein binding. Total blood lymphocyte counts and heart rate were serially monitored to assess pharmacologic responses to FTY720. Peak FTY720 blood concentrations were similar across groups. Oral clearance (CL/F) was reduced 10% in mild hepatic impairment (P = .493) and 31% in moderate hepatic impairment (P = .034). There were no significant differences in blood exposure to the hexanoic or butanoic acid metabolites among groups. The effect of FTY720 on blood lymphocytes was similar across groups, with a mean decrease of 44% from the predose value. Like-wise, the effect of FTY720 on supine heart rate was similar across groups, with a mean 13% decrease from the predose rate occurring 2 to 4 hours postdose and recovering within 1 to 2 days. Although hepatic impairment elicited changes in the disposition of FTY720, the magnitude of these changes suggests that the FTY720 dose does not need to be adjusted in mild or moderate hepatic-impaired patients.
PHYSICOCHEMICAL STUDIES OF THE CARCINOEMBRYONIC ANTIGENS OF THE HUMAN DIGESTIVE SYSTEM (1968)

A procedure has been described for the purification of the carcinoembryonic antigens (CEA) of the human digestive system. Tumor tissue extraction in 0.6 M perchloric acid followed by paper block electrophoresis and column chromatography on Sephadex G-200 resulted in highly purified CEA preparations as determined by both immunological and physicochemical criteria. The properties and composition of five different purified CEA preparations derived from digestive system cancer metastases were examined. The findings demonstrated a high degree of uniformity amongst these samples. Sedimentation coefficients ranged from 6.9 to 8S. Each sample showed the presence of 14 different amino acid residues and six different carbohydrate constituents (four of which could be quantitated with the amount of material available for analyis). Studies of a purified CEA preparation from a primary hepatoma yielded results which, in some respects, differed from those obtained with the CEA samples of metastatic tumor origin. The implications of these variations were discussed with regard to the probable presence of non-CEA components in the hepatoma preparation. Of primary importance was the observation that the few normal adult digestive system tissues tested failed to show the presence of constituents similar to the CEA. This finding would seem to indicate that, in the adult, the carcinoembryonic antigens of the human digestive system are qualitatively tumor-specific and are not dectectable in comparable normal tissues.
Different Stroke Volumes for the Left and Right Ventricles in the Moving-Actuator Type Total Artificial Heart (1993)

A new electromechanical moving-actuator type total artificial heart (TAH) has been developed to solve the imbalance problem without an extra compliance chamber. A different stroke volume was achieved by the large left sac size and the asymmetry of the actuator motion referred to the center position. The left ventricle consists of a double sac with the outer sac attached to the actuator providing active diastolic filling, while the double sac of the right ventricle being free from the actuator, and having sufficient suction produced due to the rigid pump housing. The stroke volume difference between the left and right sac is compensated through the air in the interventricular space of the variable volume (VV) space. Computer simulation based on the geometrical relationships between the blood sacs and the actuator was performed to simulate the physical mechanisms of the moving-actuator type TAH. Results were then compared with the measured pressure changes in various chambers of the pump and the stroke volume differences in mock circulation test. In two acute calf experiments, the balanced left and right atrial pressures were achieved in the moving-actuator type TAH without an extra compliance chamber.
Establishment and cryopreservation of a skin fibroblast cell line derived from Yunnan semi-fine wool sheep in the presence of synthetic ice blocker. (2014)

In this study, the fibroblasts cell line derived from ear marginal tissue of Yunnan semi-fine wool sheep was successfully established using the primary explants technique and cryopreservation technology. Additionally, the protective effect of synthetic ice blocker (SIB) including 1, 3-cyclohexanediol (1, 3-CHD) and 1, 4-cyclohexanediol (1, 4-CHD) on frozen fibroblast cells was also assessed and compared. Propidium iodide (PI) was used to stain the dead cells following cryopreservation and thawing. The results showed that compared with Medium 199 (M199) and Dulbecco's modified Eagle's medium : Nutrient Mixture F-12 (1 : 1) Mixture (DMEM/F12), Dulbecco's modified Eagle's medium (DMEM) may be more suitable for the primary culture of fibroblast cells of Yunnan semi-fine wool sheep. The growth curve of cells is a typical "S" type. After subculture for four days, the cells entered the plateau phase and began to degenerate. Biological analysis showed that the population doubling time (PDT) for subculturing fibroblast cells was approximately 26h. The Karyotyping data indicated that the percentage of fibroblast cells with normal chromosome number 2n = 54 was over 90% following subculture for 10 passages. Moreover, the tests for bacteria, fungi, viruses and mycoplasma were negative. After serial subculture for 5 generations, the fibroblast cells were cryopreserved in the presence or absence of 1, 3-CHD or 1, 4-CHD. The data indicated that with increase of the synthetic ice blocker concentrations, the viability of frozen-thawed fibroblast cells was firstly increased and then decreased. When the concentration of 1, 3-CHD or 1, 4-CHD was 50 mM, the viable percentage of frozen-thawed fibroblast cells was 91.93% +/- 2.24% and 94.13% +/- 0.55% respectively and significantly higher than that of the cells frozen in the absence of synthetic ice blockers (88.10% +/- 1.49%, P < 0.05). In conclusion, the skin fibroblast cell line of Yunnan semi-fine wool sheep was firstly established in this study. Additionally, the presence of synthetic ice blocker can increase the viability of frozen-thawed sheep fibroblast cell line.
A Real-Time Hybrid Optical System for Pattern Recognition Applications (1977)

A description of a coherent optical processor which utilizes matched spatial filters in order to do pattern recognition is presented. The processor has been interfaced to a PDP-11-40 computer which controls the input film drive, the filter stage stepper motors, digitizes, and stores data and is used for data analysis. On-line to the computer are various peripherals including: a DEC-writer, a storage scope, a plotter, and a display terminal. As an example of a pattern recognition problem, we discuss the application of the system to the identification of biological specimens.
Electrochemical Flow-Cell Setup for In Situ X-ray Investigations (2016)

A unique electrochemical three-electrode flow-cell design is presented for in situ small-angle X-ray scattering experiments on a multi-purpose laboratory X-ray diffractometer. An electrolyte layer thickness of 2 mm enables sufficient photon transmission to acquire in situ scattering curves at high signal-to-noise ratio within less than one hour despite the restricted photon flux from a standard Cu X-ray tube. Complete tightness of the cell allows electrolyte flow with controlled gas saturation in order to guarantee constant experimental conditions even for long experimental protocols. Good electrochemical performance is achieved by a special arrangement of working and counter electrodes that are deposited on the opposing X-ray transmission windows of the cell. The functionality and reliability of the cell are demonstrated in an in situ small-angle X-ray scattering study of the degradation properties of carbon-supported Pt nanoparticles during electrochemical high-potential cycling. Careful subtraction of background scattering and absolute normalization of the scattering curves yield absolute quantitative structural information about the Pt nanoparticle phase at different stages of the degradation protocol, bringing insights into the real-time evolution during electrochemical characterization.
Exercise Radionuclide Ventriculography: Practical Considerations and Sensitivity of Coronary Artery Disease Detection (1979)

Eighty-nine patients were evaluated for coronary artery disease (CAD) with exercise radionuclide ventriculography (ERV) and contrast coronary angiography. In 70 patients with documented lesions the ERV was abnormal in 65 for a sensitivity of 93%. In patients with normal coronary arteries, the ERV was abnormal in none for a specificity of 100%. Sensitivity of ERV for detecting CAD was affected by the level of exercise achieved. In patients with documented CAD who achieved adequate exercise (i.e., pressure rate product (PRP) greater than 250 or the development of angina or ST segment depression during exercise), the sensitivity was 98% (56 of 57 patients). In those with documented CAD who failed to achieve adequate exercise, the sensitivity was 69% (9 of 13 patients).
Closed-form blind identification of MIMO channels (2002)

We present a closed-form algorithm for blind identification of multiple-input/multiple-output (MIMO) finite-impulse response (FIR) systems driven by digital sources. The algorithm is based on second-order statistics and yields an asymptotically exact estimate of the MIMO channel. We assign distinct spectral signatures to each user through transmitter correlative filters, and exploit this spectral asymmetry to derive the closed-form solution. Simulation results illustrate the good performance of the proposed approach. We compare the mean-square error (MSE) of the MIMO channel estimate against the Cramer-Rao bound, and assess the algorithm capability in rejecting inter-user crosstalk interference.
Supratentorial anaplastic gliomas in adults (1989)

A retrospective analysis is presented of factors affecting the length of survival of 285 consecutive adults with newly diagnosed biopsy-proven supratentorial anaplastic glioma (188 cases of glioblastoma multiforme, 76 of anaplastic astrocytoma, 11 of anaplastic mixed glioma, and 10 of anaplastic oligodendroglioma) treated at a regional cancer center from July, 1982, through December, 1987. The approach to initial therapy included maximum feasible resection and radiotherapy. The median survival time for all patients was 35 weeks. Multivariate analysis demonstrated that age, duration of symptoms, preirradiation performance status, tumor histology, accessibility to resection, extent of resection, radiotherapy, and prior low-grade glioma were significant independent variables influencing survival. The prognostic importance of age, duration of symptoms, performance status, and tumor histology are already recognized, but three "new" findings are reported. First, patients with anaplastic oligodendroglioma had the longest median survival time (278 weeks). Second, corrected for accessibility and all other variables, patients with gross total resection lived longer than those with partial resection, and patients with any degree of resection lived longer than those who underwent only a biopsy procedure. Third, patients with anaplastic glioma in whom there was a prior history of low-grade glioma lived significantly longer after the diagnosis of anaplastic glioma than did patients in whom the anaplastic glioma apparently arose de novo.
Rate-Optimal DSP Synthesis by Pipeline and Minimum Unfolding (2005)

This paper presents a rate-optimal scheduling for real-time DSP algorithms. By using pipelining and unfolding techniques, the parallel characteristics of recursive DSP algorithms can be exploited. A novel unfolding technique is developed to unravel all concurrency in the recursive data flow graph. A perfect rate unfolded data flow graph is also introduced, which can cause a fully static rate optimal functional pipeline schedule. Experimental results have shown that the proposed method can always yield rate-optimal designs with a smaller unfolding factor compared to previous studies. >
Gld and Lpr Mice: Single Gene Mutant Models for Failed Self Tolerance (1994)

Mice homozygous for the gld or lpr mutations develop autoimmunity, and a lymphoproliferative disorder involving accumulation of huge numbers of unusual CD4-CD8-TCR alpha beta lo T cells. Here we review our past work with gld mice, and attempt to explain lymphoproliferation in terms of current models of T cell maturation and self-tolerance induction. The availability of molecular probes to the gene products of lpr and gld should shortly lead to a better understanding of the acquisition of self tolerance during T cell maturation and of autoimmunity.
Human ribonucleotide reductase M2 subunit gene amplification and transcriptional regulation in a homogeneous staining chromosome region responsible for the mechanism of drug resistance (2001)

In our previous publication it was shown that a Gemcitabine-resistant KBGem clone derived from step-wise exposure to Gemcitabine resulted in overexpression of the human Ribonucleotide Reductase M2 subunit (hRRM2) mRNA and protein (Goan et al., 1999). In this study we confirm these results and show that the hRRM2 gene amplification arises in a homogeneous staining region (hsr) derived from chromosome translocation. The hydroxyurea-resistant clone (KBHURs) was studied as a comparison. PCR analysis of the hRRM2 gene promoter confirmed the amplification. Northern and Western blots were further employed to confirm the gene amplification and hRRM2 mRNA and protein expression were compatible with the level of drug resistance. Cells synchronized by serum starvation and then returned to serum-containing growth conditions showed a rapid induction of high levels of transcription of the hRRM2 gene. To clarify whether expression of hRRM2 mRNA was regulated at a transcriptional level, several transcription factors, including AP-1, Sp1, AP-2, CREB, NF-kappa B, and OCT1, were examined by gel-shift assay. Interestingly, the KBGem clone was regulated by different transcription factors than the KBHURs clone. Compared to the wild-type KB cells (KBwt), the KBGem clone exhibited a different binding pattern for Sp1 and NF-kappa B. The KBHURs clone, however, demonstrated a unique binding pattern with AP-1 and CREB, different from the KBwt control as well as the KBGem clone. Therefore, we conclude that the drug-resistant phenotype is associated with human RRM2 gene amplification from a homogeneous staining chromosome region and altered transcription regulation. Each clone demonstrated a unique pattern of transcription factor binding that may play a vital role in the mechanism of drug resistance.