gebhart/patrepeval huggingface dataset:
Antimyeloma activity of heat shock protein-90 inhibition (2005)

We show that multiple myeloma (MM), the second most commonly diagnosed hematologic malignancy, is responsive to hsp90 inhibitors in vitro and in a clinically relevant orthotopic in vivo model, even though this disease does not depend on HER2/neu, bcr/abl, androgen or estrogen receptors, or other hsp90 chaperoning clients which are hallmarks of tumor types traditionally viewed as attractive clinical settings for use of hsp90 inhibitors, such as the geldanamycin analog 17-AAG. This class of agents simultaneously suppresses in MM cells the expression and/or function of multiple levels of insulin-like growth factor receptor (IGF-1R) and interleukin-6 receptor (IL-6R) signaling (eg, IKK/NF-kappaB, PI-3K/Akt, and Raf/MAPK) and downstream effectors (eg, proteasome, telomerase, and HIF-1alpha activities). These pleiotropic proapoptotic effects allow hsp90 inhibitors to abrogate bone marrow stromal cell-derived protection on MM tumor cells, and sensitize them to other anticancer agents, including cytotoxic chemotherapy and the proteasome inhibitor bortezomib. These results indicate that hsp90 can be targeted therapeutically in neoplasias that may not express or depend on molecules previously considered to be the main hsp90 client proteins. This suggests a more general role for hsp90 in chaperoning tumor- or tissue-type-specific constellations of client proteins with critical involvement in proliferative and antiapoptotic cellular responses, and paves the way for more extensive future therapeutic applications of hsp90 inhibition in diverse neoplasias, including MM.
Role of Nitric Oxide in the Renal Protective Effects of Ischemic Preconditioning (2003)

Possible involvement of nitric oxide (NO) in the protective effect of ischemic preconditioning against the ischemia/reperfusion-induced acute renal failure was investigated. Ischemic preconditioning, which consists of three cycles of 2-minute ischemia followed by 5-minute reperfusion, was performed prior to 45-minute ischemia. Ischemic preconditioning significantly improved the renal dysfunction induced by 45-minute ischemia followed by 24-hour reperfusion. Histopathological examination of the kidney of ischemia/reperfusion rats revealed severe renal damage, and suppression of the damage was seen with the ischemic preconditioning treatment. NO metabolites (NOx) production in the kidney after 45-minute ischemia and reperfusion was markedly increased in ischemia/reperfusion rats with ischemic preconditioning, compared with animals not subjected to ischemic preconditioning, and these increases correlated with changes in endothelial NO synthase (eNOS) protein expression in renal tissues. The improvement of renal dysfunction in ischemic preconditioning rats was abolished by the pretreatment with NG-nitro-L-arginine, a nonselective NOS inhibitor, but not with aminoguanidine, an inducible NOS inhibitor. In addition, increment of endothelin-1 (ET-1) content in the kidney after the reperfusion was markedly suppressed by ischemic preconditioning treatment. These findings suggest that the protective effect of ischemic preconditioning on ischemia/reperfusion -induced acute renal failure is closely related to the renal nitric oxide production following the increase in eNOS expression after the reperfusion and that the suppressive effect of ischemic preconditioning on the ischemia/reperfusion -induced renal ET-1 overproduction may be partly involved in the ameliorating effect of ischemic preconditioning.
A human skin multifunctional O-acyltransferase that catalyzes the synthesis of acylglycerols, waxes, and retinyl esters (2005)

Acyl-CoA-dependent O-acyltransferases catalyze reactions in which fatty acyl-CoAs are joined to acyl acceptors containing free hydroxyl groups to produce neutral lipids. In this report, we characterize a human multifunctional O-acyltransferase (designated MFAT) that belongs to the acyl-CoA:diacylglycerol acyltransferase 2/acyl-CoA:monoacylglycerol acyltransferase (MGAT) gene family and is highly expressed in the skin. Membranes of insect cells and homogenates of mammalian cells overexpressing MFAT exhibited significantly increased MGAT, acyl-CoA:fatty acyl alcohol acyltransferase (wax synthase), and acyl-CoA:retinol acyltransferase (ARAT) activities, which catalyze the synthesis of diacylglycerols, wax monoesters, and retinyl esters, respectively. Furthermore, when provided with the appropriate substrates, intact mammalian cells overexpressing MFAT accumulated more waxes and retinyl esters than control cells. We conclude that MFAT is a multifunctional acyltransferase that likely plays an important role in lipid metabolism in human skin.
Multiple transformation ofSaccharomyces cerevisiaeby protoplast fusion (1992)

A technique for the multiple transformation of yeast by protoplast fusion is described. This involved the PEG-induced fusion of protoplasts from cells which had been treated with chromosome-fragmenting agents (in this case cupferron and hydroxylamine) with protoplasts of triply auxotrophic cells. The recovery of transformants was increased significantly if one of the amino acid requirements of the recipient strain was included in the selection medium. Transformants isolated on supplemented media remained auxotrophic for that requirement. Prototrophic, uninucleate transformants had a DNA content and cellular volume similar to that of the parental strains. Possible mechanisms of gene transfer are discussed. This technique offers the possibility of transferring desirable characteristics from one yeast strain to another without altering the ploidy level of the recipient strain.
PCR-Based Assay To Quantify Human Immunodeficiency Virus Type 1 DNA in Peripheral Blood Mononuclear Cells (2000)

An assay that quantifies the amount of human immunodeficiency virus type 1 (HIV-1) DNA in peripheral blood mononuclear cells has been developed. PCR amplification of the HIV-1 DNA is performed in the presence of an internal quantitation standard, and colorimetric detection of the amplified product is performed with microwell plates. The copies of HIV-1 DNA are normalized to total genomic DNA input. The assay has an analytical sensitivity of 10 input copies per amplification reaction and a three-log detection range. In an analysis of sequential samples from patients on combination therapy, HIV-1 DNA was quantifiable for all individuals tested, including those with undetectable plasma HIV-1 RNA. In a separate study, a comparison of HIV-1 DNA levels was made with a group of long-term survivors and progressors. The mean HIV-1 DNA levels were lower in the long-term survivors than in the progressors (P, 0.04). The mean HIV-1 RNA levels were also lower, but the difference was not statistically significant (P, 0.164). A quantitative DNA assay will provide an additional tool to gain insight into the natural history of infection and the continued efficacy of potent antiretroviral therapies.
Effect of growth stage on mycolic acid structure in cell walls of Nocardia asteroides GUH-2 (1988)

Mycolic acids were extracted from the cell walls of Nocardia asteroides GUH-2 during different phases of growth at 37 degrees C. These were subjected to structural analysis by combining thin-layer chromatography and gas-liquid chromatography with UV and infrared spectrophotometry and mass spectroscopy of both methyl esters and trimethyl silyl derivatives. By analyzing the fragmentation patterns of these derivatives by three different methods of mass spectroscopy combined with gas-liquid chromatographic separation, the different structural subclasses of mycolic acids were quantitated. Significant qualitative and quantitative modifications of specific mycolic acid subclasses occurred in the cell walls of N. asteroides GUH-2 that were growth stage dependent. The mycolic acids that were predominant in the log phase were polyunsaturated (greater than 2 double bonds per molecule), with long chain lengths and even carbon atom numbers (i.e., C54, C56). In contrast, those that were prominent in the stationary phase were more saturated (few or no double bonds) and of shorter overall carbon chain length (less than or equal to C52). Furthermore, stationary-phase cells had significantly increased amounts of mycolic acids with odd-numbered carbon chain lengths (i.e., C49, C51, C53).
Link and system performance aspects of proportional fair scheduling in WCDMA/HSDPA (2003)

In this paper, the capability of proportional fair (P-FR) packet scheduling for WCDMA/HSDPA is studied considering inherent limitations and system conditions. Specifically, issues of link adaptation dynamic range, power and code resources, convergence settings, signaling overhead, and code multiplexing are studied. Although the P-FR method may ideally offer around 100% capacity gain compared to blind scheduling, this gain largely depends on the operating conditions.
The LAMBDANET multiwavelength network: architecture, applications, and demonstrations (1990)

A summary is presented of research conducted over the last few years concerning the LAMBDANET multiwavelength optical network. Descriptions are given of some variations, including several applications based on these architectures. Experimental results demonstrate the technological feasibility of this approach. The LAMBDANET design incorporates three basic ingredients: (1) it associates a unique optical wavelength with each transmitting node in a cluster of nodes; (2) the physical topology is that of a broadcast star; and (3) each receiving node identifies transmitting nodes based on the transmission wavelength through wavelength demultiplexing. This network design features full connectivity among the nodes, large nonblocking throughput, data format transparency, and flexible control. The LAMBDANET network is used for both point-to-point and point-to-multipoint applications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Reconstitution of G 1 Cyclin Ubiquitination with Complexes Containing SCF Grr1 and Rbx1 (1999)

Control of cyclin levels is critical for proper cell cycle regulation. In yeast, the stability of the G1 cyclin Cln1 is controlled by phosphorylation-dependent ubiquitination. Here it is shown that this reaction can be reconstituted in vitro with an SCF E3 ubiquitin ligase complex. Phosphorylated Cln1 was ubiquitinated by SCF (Skp1-Cdc53-F-box protein) complexes containing the F-box protein Grr1, Rbx1, and the E2 Cdc34. Rbx1 promotes association of Cdc34 with Cdc53 and stimulates Cdc34 auto-ubiquitination in the context of Cdc53 or SCF complexes. Rbx1, which is also a component of the von Hippel-Lindau tumor suppressor complex, may define a previously unrecognized class of E3-associated proteins.
REVIEW Role of Transforming Growth Factor- Signaling in Cancer (2015)

Signaling from transforming growth factor- (TGF-) through its unique transmembrane receptor serine– threonine kinases plays a complex role in carcinogenesis, having both tumor suppressor and oncogenic activities. Tu-mor cells often escape from the antiproliferative effects of TGF- by mutational inactivation or dysregulated expres-sion of components in its signaling pathway. Decreased re-ceptor function and altered ratios of the TGF- type I and type II receptors found in many tumor cells compromise the tumor suppressor activities of TGF- and enable its onco-genic functions. Recent identification of a family of intracel-lular mediators, the Smads, has provided new paradigms for understanding mechanisms of subversion of TGF- signal-ing by tumor cells. In addition, several proteins recently have been identified that can modulate the Smad-signaling
The development of stable protein formulations: a close look at protein aggregation, deamidation, and oxidation. (1993)

The biochemical literature has been surveyed to present an overview of the three most common protein degradation pathways: protein aggregation, deamidation, and oxidation. The mechanisms for each of these degradation routes are discussed with particular attention given to the effect of formulation conditions such as pH, ionic strength, temperature, and buffer composition. Strategies to reduce protein degradation are also discussed. These strategies are based on an understanding of the degradation mechanisms and the effect of changes in the storage conditions and formulation components on the degradation. The effects of each of the degradation routes on pharmaceutically relevant properties such as biological activity, metabolic half-life, and immunogenicity are summarized. Predicting a priori the alteration of pharmaceutical properties caused by the three degradation routes is difficult, and must be determined on a case-by-case basis for each protein. The difficulty in predicting the effect of degradation and analyzing the temperature dependence of reaction rates in proteins results in longer development times for protein formulations than for small molecule formulations. Although the use of accelerated stability to predict protein shelf life is difficult, conditions are discussed whereby the Arrhenius equation can be used to shorten formulation development time.
SERUM LEVELS OF SHED HER2/NEU PROTEIN IN MEN WITH PROSTATE CANCER CORRELATE WITH DISEASE PROGRESSION (2005)

Increased serum Her-2/neu correlates with the presence of metastatic disease and it may indicate an increased risk of death in patients with castrate, metastatic prostate cancer. The detection of serum Her-2/neu is a minimally invasive alternative to tumor sampling for identifying potential candidates for anti-Her-2/neu treatment strategies. Further studies are needed to optimize this assay for application in the clinical setting.
Adaptive streaming of MPEG video over IP networks (2002)

The authors present the design of an adaptive service for streaming MPEG video over a best-effort IP network environment. The adaptive video streaming service exploits the inherent adaptiveness of video applications to perform controlled and graceful adjustments to the perceptual quality of the displayed MPEG video stream in response to fluctuations in the QoS delivered by the three primary components in the end-to-end path of a video stream, i.e., the video server, the network, and the receiver. The design supports multiple video adaptation techniques that can be applied individually or in combination to adapt the transmitted video stream in response to fluctuations in the QoS provided by the underlying system. A novel aspect of the design is a video adaptation algorithm that selects the adaptation delivering the best perceptual quality for the video playback for a given QoS delivered by the underlying infrastructure. They describe a prototype implementation of the adaptive video streaming service and present the results of a performance evaluation of this prototype system.
Trace reconstruction with constant deletion probability and related results (2008)

We provide several new results for the trace reconstruction problem. In this setting, a binary string yields a collection of traces, where each trace is independently obtained by independently deleting each bit with a fixed probability Δ. Each trace therefore consists of a random subsequence of the original sequence. Given the traces, we wish to reconstruct the original string with high probability. The questions are how many traces are necessary for reconstruction, and how efficiently can the reconstruction be performed. Our primary result is that for some universal constant γ and uniformly chosen strings of length n, for any Δ n) traces in poly(n) time with high probability. We also obtain algorithms that require a number of traces exponential in O (√n) for any Δ
THE ROLE OF OXYGEN FREE RADICALS IN MEDIATING THE REPERFUSION INJURY OF COLD-PRESERVED ISCHEMIC KIDNEYS1,2 (1985)

We evaluated the hypothesis that postischemic renal failure is caused primarily at reperfusion by oxygen-derived free radicals in a swine model designed to realistically mimick human cadaveric renal transplantation. Both kidneys were removed, flushed with Euro-Collins solution, stored 24 hr at 4 degrees C, and then transplanted to a second pig. Experiments were paired, each pig receiving one treated and one control kidney. All pigs received the optimal conventional regimen of hydration, phenoxybenzamine, furosemide, and mannitol to allow assessment of free radical treatment superimposed thereupon. Two days later creatinine clearance (CCR) was measured from each kidney via separate ureterostomies. Untreated kidneys developed severe functional impairment, CCR falling from a normal level of 25.5 +/- 6.3 ml/min (n = 8) to 7.7 +/- 0.9 ml/min (n = 14, P less than .05 vs. control). The infusion of 20 mg of the free radical scavenger superoxide dismutase (SOD) into the renal artery at reperfusion substantially ameliorated this injury (CCR = 15.9 +/- 1.7 ml/min, n = 18, P less than 0.05 vs. control). A dose-response curve to SOD showed no effect of doses of 0.2 mg (CCR = 8.0 +/- 1.1 ml/min, n = 4) or 2 mg (CCR = 7.7 +/- 0.9, n = 5), and no greater benefit from 100 mg (CCR = 16.1 +/- 2.1 ml/min, n = 3, P less than 0.05 vs. control). Blocking the generation of superoxide radicals from xanthine oxidase with allopurinol (50 mg/kg) afforded similar protection (CCR = 18.2 +/- 1.8; n = 11, P less than 0.01 vs. control). On the other hand, following an 18-hr period of cold ischemia, little damage was sustained by the untreated (control) kidneys (CCR = 22.1 +/- 0.6 ml/min). Consequently, under these conditions the ablation of free radical generation with allopurinol provided no significant benefit. These findings suggest that after a critical period of cold ischemic preservation, metabolic changes take place within the kidney that lead to free radical generation and consequent tissue injury upon reperfusion, despite optimal preservation by conventional methods. This damage can be prevented by simple nontoxic measures--which, therefore, show great promise for use in the prevention of early renal failure following cadaveric renal transplantation.
The teratogenic Veratrum alkaloid cyclopamine inhibits Sonic hedgehog signal transduction (1998)

The steroidal alkaloid cyclopamine produces cyclopia and holoprosencephaly when administered to gastrulation-stage amniote embryos. Cyclopamine-induced malformations in chick embryos are associated with interruption of Sonic hedgehog (Shh)-mediated dorsoventral patterning of the neural tube and somites. Cell types normally induced in the ventral neural tube by Shh are either absent or appear aberrantly at the ventral midline after cyclopamine treatment, while dorsal cell types normally repressed by Shh appear ventrally. Somites in cyclopamine-treated embryos show Pax7 expression throughout, indicating failure of sclerotome induction. Cyclopamine at concentrations of 20-100 nM blocks the response of neural plate explants to recombinant Shh-N in a dose-dependent manner. Similar concentrations have no effect on the post-translational modification of Shh by cholesterol in transfected COS-1 cells. Comparison of the effects of cyclopamine to those of the holoprosencephaly-inducing cholesterol synthesis inhibitor AY-9944 shows that cyclopamine does not induce malformations by interfering with cholesterol metabolism. Although AY-9944 does not interrupt Shh signaling in ovo, it blocks the response to Shh-N in explants cultured without an exogenous cholesterol source. As predicted by current models of the regulation of cholesterol metabolism, the response to Shh-N in AY-9944-treated explants is restored by providing exogenous cholesterol. However, exogenous cholesterol does not restore Shh signaling in cyclopamine-treated explants. These findings suggest that cyclopamine-induced teratogenesis is due to a more direct antagonism of Shh signal transduction.
Allelic Imbalance in Primary Breast Carcinomas and Metastatic Tumors of the Axillary Lymph Nodes (2005)

Axillary lymph node status is the most important prognostic factor in predicting disease outcome in women with breast cancer. A number of chromosomal aberrations in primary breast tumors have been correlated with lymph node status and clinical outcome, but chromosomal changes particular to metastatic lymph node tumors have not been well studied. DNA samples isolated from laser-microdissected primary breast and metastatic axillary lymph node tumors from 25 women with invasive breast cancer were amplified using 52 microsatellite markers defining 26 chromosomal regions commonly deleted in breast cancer. Levels and patterns of allelic imbalance (AI) within and between breast and lymph node tumors were assessed to identify chromosomal alterations unique to primary or metastatic tumors and to examine the timing of metastatic potential. The overall frequency of AI in primary breast tumors (0.24) was significantly greater (P < 0.001) than that in lymph node tumors (0.10), and congruent AI events were observed for < 20% of informative markers. AI at chromosomes 11q23.3 and 17p13.3 occurred significantly more frequently (P < 0.05) in primary breast tumors alone; no chromosomal regions showed a significantly higher AI frequency in lymph nodes. Higher rates of AI in primary versus metastatic lymph node tumors suggest that acquisition of metastatic potential may be an early event in carcinogenesis, occurring before significant levels of AI accumulate in the primary tumor. In addition, patterns of AI were highly discordant between tumor types, suggesting that additional genetic alterations accumulated independently in the two cell populations.
Curves and Surfaces for Computer Aided Geometric Design--A Practical Guide. (1990)

From the Publisher:
This book will be of interest to computer graphics enthusiasts, software developers for CAD/CAM systems, geometric modeling researchers, graphics programmers, academicians, and many others throughout the graphics community. Assuming only a background in calculus and basic linear algebra, the author's informal and reader-friendly style makes the material accessible to a wide audience. Finally, the included disk contains data sets and all of the C programs used in the book, making it easier for the user to gain first-hand experience with the concepts as they are explained. This unified treatment of curve and surface design concepts focuses on Bezier and B-spline methods for curves, rational Bezier and B-spline curves, geometric continuity, spline interpolation, and Coons methods. The fourth edition has been thoroughly updated and revised to include a new chapter on recursive subdivision, as well as new sections on triangulations and scattered data interpolants. Finally, the disk in the back of the book has been updated to include all of the programs, as well as the data sets from the text.
A scaling methodology for oxide-nitride-oxide interpoly dielectric for EPROM applications (1990)

This scaling scheme is based on a charge retention model which successfully explains the observed charge loss phenomena of an advanced erasable programmable read-only memory (EPROM) cell with an oxide-nitride-oxide (ONO) film as the interpoly dielectric. It is shown that there are three distinct phases in EPROM charge retention characteristics. The main sources of charge loss are charge movement in the nitride and charge leakage out of the ONO film. The charge loss can be dramatically reduced by thinning the nitride and thickening the top and bottom oxides. The resultant interpoly ONO film shows much smaller current leakage and superior charge retention capability.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>