gebhart/patrepeval huggingface dataset:
Multifactorial mechanisms associated with broad cross-resistance of ovarian carcinoma cells selected by cyanomorpholino doxorubicin. (1991)

The cyanomorpholino derivative of doxorubicin (MRA-CN) is a DNA intercalator and alkylator that is a highly potent cytotoxin, non-cross-resistant in multidrug-resistant cells, and noncardiotoxic in comparison with doxorubicin. To further examine mechanisms of action and resistance to MRA-CN, a cell line resistant to MRA-CN, ES-2R, was established by growing a human ovarian carcinoma cell line, ES-2, in increasing concentrations of the drug. The resistant subline was 4-fold resistant to MRA-CN and cross-resistant to other DNA cross-linking agents, cisplatin (7-fold) and carmustine (3-fold), as well as to the DNA strand-breaking agents etoposide (6-fold), doxorubicin (2-fold), bleomycin (5-fold), and ionizing radiation (2-fold). In contrast, ES-2R cells were not cross-resistant to vinblastine. Several months of additional growth of ES-2R cells in MRA-CN did not yield higher, stable levels of drug resistance. A low level of P-glycoprotein was detectable in the ES-2R cells. However, the extent of intracellular accumulation of [3H]MRA-CN by this resistant cell line was identical to that of the sensitive line. The number of DNA cross-links formed by cisplatin in ES-2R was only 50% of that of the ES-2 cells and was associated with a 50% increase in the rate of repair of these cross-links in the resistant cells. Ionizing radiation induced similar amounts of single- and double-strand breaks in the ES-2 line as well as in the ES-2R cells. There was no apparent difference between the two cell lines in the rate and extent of repair of these DNA breaks. Thus, enhanced DNA repair cannot explain the phenomenon of cross-resistance to radiation. Comparisons of glutathione (GSH) content and the enzymes involved in GSH homeostasis showed significant differences. Resistant cells contained 1.5-fold more GSH, a 2.2-fold increase in gamma-glutamyltranspeptidase activity, and a 2.4-fold increase in GSH reductase compared with ES-2 cells (all P less than 0.05). Total glutathione-S-transferase (GST) activity was 2.6-fold higher (P less than 0.01) in the ES-2R line. The pi-class GST subunit by Western blotting and GST activity toward ethacrynic acid were increased 2-fold in the resistant cells. Depletion of GSH levels in ES-2R cells by buthionine sulfoximine restored the sensitivity of ES-2R to MRA-CN. These findings implicate a role for GSH metabolism in the resistance phenotype of ES-2R cells. We have previously reported that these cells have an increased generation time and decreased topoisomerase II content. Thus, the ES-2R cell line exhibits a complex phenotype of broad cross-resistance, which is likely to involve multiple mechanisms, and includes enhanced DNA repair and increased GSH content and GST activity.
Cloning and expression of a cytosolic megakaryocyte protein-tyrosine-phosphatase with sequence homology to retinaldehyde-binding protein and yeast SEC14p. (1992)

Protein tyrosine phosphorylation is important in the regulation of cell growth, the cell cycle, and malignant transformation. We have cloned a cDNA that encodes a cytosolic protein-tyrosine-phosphatase (PTPase), MEG2, from MEG-01 cell and human umbilical vein endothelial cell cDNA libraries. The 4-kilobase cDNA sequence of PTPase MEG2 corresponds in length to the mRNA transcript detected by Northern blotting. The predicted open reading frame encodes a 68-kDa protein composed of 593 amino acids and has no apparent signal or transmembrane sequences, suggesting that it is a cytosolic protein. The C-terminal region has a PTPase catalytic domain that has 30-40% amino acid identity to other known PTPases. The N-terminal region has 254 amino acids that are 28% identical to cellular retinaldehyde-binding protein and 24% identical to yeast SEC14p, a protein that has phosphatidylinositol transfer activity and is required for protein secretion through the Golgi complex in yeast. Recombinant PTPase MEG2 expressed in Escherichia coli possesses PTPase activity. PTPase MEG2 mRNA was detected in 12 cell lines tested, which suggests that this phosphatase is widely expressed. The structure of PTPase MEG2 implies that a tyrosine phosphatase could participate in the transfer of hydrophobic ligands or in functions of the Golgi apparatus.
Cellulite: a review of its physiology and treatment (2004)

Cellulite affects 85-98% of post-pubertal females of all races. While not a pathologic condition, it remains an issue of cosmetic concern to a great number of individuals. Despite its high prevalence, there have been few scientific investigations into the physiology of cellulite. There have only been a few dozen peer-reviewed articles devoted to cellulite in the medical literature in the past 30 years. There is no definitive explanation for its presentation. This greatly complicates the ability to treat or improve it. The four leading hypotheses that purport to explain the physiology of cellulite include: sexually dimorphic skin architecture, altered connective tissue septae, vascular changes and inflammatory factors. Treatment modalities can be divided into four main categories: attenuation of aggravating factors, physical and mechanical methods, pharmacological agents and laser. There are no truly effective treatments for cellulite.
Low-complexity near-optimal signal detection in underdetermined large-MIMO systems (2012)

In this paper, we consider signal detection in n <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> × n <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">r</sub> underdetermined MIMO (UD-MIMO) systems, where i) n <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> >; n <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">r</sub> with a overload factor α = n <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> over n <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">r</sub> >; 1, ii) n <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> symbols are transmitted per channel use through spatial multiplexing, and iii) n <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> , n <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">r</sub> are large (in the range of tens). A low-complexity detection algorithm based on reactive tabu search is considered. A variable threshold based stopping criterion is proposed which offers near-optimal performance in large UD-MIMO systems at low complexities. A lower bound on the maximum likelihood (ML) bit error performance of large UD-MIMO systems is also obtained for comparison. The proposed algorithm is shown to achieve BER performance close to the ML lower bound within 0.6 dB at an uncoded BER of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-2</sup> in 16 × 8 V-BLAST UD-MIMO system with 4-QAM (32 bps/Hz). Similar near-ML performance results are shown for 32 × 16, 32 × 24 V-BLAST UD-MIMO with 4-QAM/16-QAM as well. A performance and complexity comparison between the proposed algorithm and the λ-generalized sphere decoder (λ-GSD) algorithm for UD-MIMO shows that the proposed algorithm achieves almost the same performance of λ-GSD but at a significantly lesser complexity.
Hydrogen Desorption Exceeding Ten Weight Percent from the New Quaternary Hydride Li3BN2H8 (2004)

Mobile applications of hydrogen power have long demanded new solid hydride materials with large hydrogen storage capacities. We report synthesis of a new quaternary hydride having the approximate composition Li(3)BN(2)H(8) with 11.9 wt % theoretical hydrogen capacity. It forms by reacting LiNH(2) and LiBH(4) powders in a 2:1 molar ratio either by ball milling or by heating the mixed powders above 95 degrees C. This new quaternary hydride melts at approximately 190 degrees C and releases > or =10 wt % hydrogen above approximately 250 degrees C. A small amount of ammonia (2-3 mol % of the generated gas) is released simultaneously. Preliminary calorimetric measurements suggest that hydrogen release is exothermic and, hence, not easily reversible.
Activation of platelets by modified C-reactive protein. (1982)

The functional similarities between C-reactive protein (CRP) and immunoglobulin raised the possibility that modified CRP might resemble immunoglobulin in its activating effects upon the human platelet. Thermally-aggregated CRP (H-CRP), but not unmodified CRP, induced reactions of aggregation and secretion from isolated platelets; maximum responses occurred with less than 50 microgram/ml H-CRP and were similar to responses mediated by thermally-aggregated human IgG (AHGG). Platelet activation induced by H-CRP was sensitive to the presence of EDTA and dibucaine, required metabolic energy and was inhibited by increased levels of cAMP. Like AHGG, H-CRP acted synergistically with other platelet stimulators, although on a weight basis H-CRP appeared approximately ten- to twenty-fold more effective than AHGG. Complexes formed between CRP and certain of its polycationic ligands (PLL and protamine) shared platelet activating properties with H-CRP, whereas complexes of CRP and CPS did not. These data point to the ability of appropriately modified CRP to stimulate or enhance platelet responsiveness, and taken together with those reactivities described previously between modified CRP and certain lymphocytes, phagocytes, and the complement system, support the concept that CRP can initiate biological activities similar to those mediated by immunoglobulin.
An analytical model for designing memory hierarchies (1996)

Memory hierarchies have long been studied by many means: system building, trace driven simulation, and mathematical analysis. Yet little help is available for the system designer wishing to quickly size the different levels in a memory hierarchy to a first order approximation. We present a simple analysis for providing this practical help and some unexpected results and intuition that come out of the analysis. By applying a specific, parameterized model of workload locality, we are able to derive a closed form solution for the optimal size of each hierarchy level. We verify the accuracy of this solution against exhaustive simulation with two case studies: a three level I/O storage hierarchy and a three level processor cache hierarchy. In all but one case, the configuration recommended by the model performs within 5% of optimal. One result of our analysis is that the first place to spend money is the cheapest (rather than the fastest) cache level, particularly with small system budgets. Another is that money spent on an n level hierarchy is spent in a fixed proportion until another level is added.
Global Patterns of Cancer Incidence and Mortality Rates and Trends (2010)

While incidence and mortality rates for most cancers (including lung, colorectum, female breast, and prostate) are decreasing in the United States and many other western countries, they are increasing in several less developed and economically transitioning countries because of adoption of unhealthy western lifestyles such as smoking and physical inactivity and consumption of calorie-dense food. Indeed, the rates for lung and colon cancers in a few of these countries have already surpassed those in the United States and other western countries. Most developing countries also continue to be disproportionately affected by cancers related to infectious agents, such as cervix, liver, and stomach cancers. The proportion of new cancer cases diagnosed in less developed countries is projected to increase from about 56% of the world total in 2008 to more than 60% in 2030 because of the increasing trends in cancer rates and expected increases in life expectancy and growth of the population. In this review, we describe these changing global incidence and mortality patterns for select common cancers and the opportunities for cancer prevention in developing countries.
Effects of Dimethylsulfoxide on the Lactose Operon in Escherichia coli (1966)

Fowler, Audree V. (University of California, Los Angeles), and Irving Zabin. Effects of dimethylsulfoxide on the lactose operon in Escherichia coli. J. Bacteriol. 92:353-357. 1966.-Dimethylsulfoxide (DMSO) at a concentration of 5% (v/v) in the culture medium inhibits the growth of Escherichia coli to only a slight extent, and does not affect the differential rate of synthesis of beta-galactosidase. Resting cells remain viable after shaking in the presence of 20% DMSO for 3 hr at 37 C. Both beta-galactosidase and thiogalactoside transacetylase retain almost all activity after incubation in even higher concentrations of the solvent for many hours. DMSO decreases the permeability barrier. The rate of hydrolysis of o-nitrophenyl-beta-d-galactoside (ONPG) in whole cells containing beta-galactosidase but lacking permease is increased in cells treated with 5% DMSO. Several permeaseless strains preinduced for beta-galactosidase will grow on lactose in the presence, but not in the absence, of 5% DMSO. When permeaseless strains are grown on tetrazolium-lactose-agar, the presence of 5% DMSO causes a definite but not marked shift toward the lactose-positive character.
Oncogenic ALK Fusion in Rare and Aggressive Subtype of Colorectal Adenocarcinoma as a Potential Therapeutic Target (2016)

Colorectal carcinoma harboring ALK fusions represent a rare aggressive subtype of colorectal carcinoma with distinct clinicopathologic features. This report provides the first clinical evidence that such patients may benefit from targeted monotherapy with ALK inhibitors. Clin Cancer Res; 22(15); 3831-40. ©2016 AACR.
Synthesis and Structure-Activity Relationships of Neuromuscular Blocking Agents (2002)

The first use of neuromuscular blocking agents (muscle relaxants) in clinical practice (1942) revolutionised the practice of anaesthesia and started the modern era of surgery. Since 1942 introduction of tubocurarine (18) neuromuscular blocking agents have been used routinely to provide skeletal muscle relaxation during surgical procedures allowing access to body cavities without hindrance from voluntary or reflex muscle movement. After the introduction of tubocurarine and the depolarizing suxamethonium chloride (4) (1949) several nondepolarizing steroidal and nonsteroidal neuromuscular blocking agents with different onset time and duration of effect were introduced e.g. gallamine triethiodide (1) (1949), methocurine (2) (1949), alcuronium chloride (3) (1963), pancuronium bromide (9) (1968), vecuronium bromide (11) (1982), pipecuronium bromide (10) (1982), atracurium besylate (5) (1982), doxacurium chloride (6) (1991), mivacurium chloride (8) (1992), rocuronium bromide (12) (1994) cisatracurium besylate (7) (1996), and rapacuronium bromide (13) (2000). SZ 1677 (14) a steroid type nondepolarizing neuromuscular blocking agent under development (preclinical phase). This review article deals with a comprehensive survey of the progress in chemical, pharmacological and, in some respects, of clinical studies of neuromuscular blocking agents used in the clinical practice and under development, including the synthesis, structure elucidation, pharmacological actions, structure activity relationships studies of steroidal and nonsteroidal derivatives.
Phenotypic Complementation Establishes Requirements for Specific POU Domain and Generic Transactivation Function of Oct-3/4 in Embryonic Stem Cells (2002)

Transcription factors of the POU family govern cell fate through combinatorial interactions with coactivators and corepressors. The POU factor Oct-3/4 can define differentiation, dedifferentation, or self-renewal of pluripotent embryonic stem (ES) cells in a sensitive, dose-dependent manner (H. Niwa, J.-I. Miyazali, and A. G. Smith, Nat. Genet. 24:372-376, 2000). Here we have developed a complementation assay based on the ability of Oct-3/4 transgenes to rescue self-renewal in conditionally null ES cells and used this to define which domains of Oct-3/4 are required to sustain the undifferentiated stem cell phenotype. Surprisingly, we found that molecules lacking either the N-terminal or C-terminal transactivation domain, though not both, can effectively replace full-length Oct-3/4. Furthermore, a fusion of the heterologous transactivation domain of Oct-2 to the Oct-3/4 POU domain can also sustain self-renewal. Thus, the unique function of Oct-3/4 in ES cell propagation resides in combination of the specific POU domain with a generic proline-rich transactivation domain. Interestingly, however, Oct-3/4 target gene expression elicited by the N- and C-terminal transactivation domains is not identical, indicating that at least one class of genes activated by Oct-3/4 is not required for ES cell propagation.
Underwater acoustic communication channels: Propagation models and statistical characterization (2009)

Acoustic propagation is characterized by three major factors: attenuation that increases with signal frequency, time-varying multipath propagation, and low speed of sound (1500 m/s). The background noise, although often characterized as Gaussian, is not white, but has a decaying power spectral density. The channel capacity depends on the distance, and may be extremely limited. Because acoustic propagation is best supported at low frequencies, although the total available bandwidth may be low, an acoustic communication system is inherently wideband in the sense that the bandwidth is not negligible with respect to its center frequency. The channel can have a sparse impulse response, where each physical path acts as a time-varying low-pass filter, and motion introduces additional Doppler spreading and shifting. Surface waves, internal turbulence, fluctuations in the sound speed, and other small-scale phenomena contribute to random signal variations. At this time, there are no standardized models for the acoustic channel fading, and experimental measurements are often made to assess the statistical properties of the channel in particular deployment sites.
Resistance of the Double-low Rapeseed Cultivar Xiangyou 15 (B. napus) to Sclerotinia sclerotiorum (2003)

By mycelia inoculation at seedling stage and mycelia-borne stick cultivar Xiangyou 15 showed the high resistance to stem rot (Sclerotinia sclerotiorum). The phenolic contents and chitinase activity increased rapidly, and maintained for a long time when the plants were infected. The progeny from the crosses of Xingyou 15 with the susceptible rapeseed variety 98C40 or moderately-resistant variety Zhongyou 821 showed midparent resistance or tendency to the resistant parent.
IQGAP2 inactivation through aberrant promoter methylation and promotion of invasion in gastric cancer cells (2007)

Invasion and metastases of cancer cells are the main causes of treatment failure in cancer. IQ motif-containing GTPase activating protein 1 (IQGAP1), plays pivotal roles in intercellular adhesion, migration, invasion and metastases in various cancer cells. However, the role of another family member, IQGAP2, in carcinogenesis remains unknown. Here, we investigated IQGAP2 functions in gastric cancers. We found that IQGAP2 protein expression was lost in 5 of the 9 gastric cancer cell lines. Through analysis by the methylation-specific PCR, aberrant IQGAP2 methylation was detected in 3 gastric cancer cell lines. IQGAP2 mRNA was found to be activated after 5-aza-2'-deoxycytidine treatment of the methylation-positive cells. Moreover, IQGAP2 methylation was detected in 28 of the 59 (47%) primary gastric cancer tissues, but not in 12 normal gastric mucosa samples. Immunohistochemical staining revealed that 7 of the 8 (88%) gastric cancer tissues without methylation signals displayed IQGAP2 expression, whereas among 10 with methylation signals none expressed IQGAP2 (p = 0.0002), indicating that IQGAP2 methylation is highly associated with loss of the IQGAP2 expression in the primary gastric cancer tissues as well as gastric cancer cell lines. Furthermore, IQGAP2 methylation was also associated with tumor invasion and a poor prognosis. IQGAP2 knockdown with small interfering RNA increased the invasive capacity of a gastric cancer cell line. These results suggest that silencing of IQGAP2 by promoter methylation may contribute to gastric cancer development.
Positive Selection at Reproductive ADAM Genes with Potential Intercellular Binding Activity (2004)

Many genes with a role in reproduction, including those implicated in fertilization and spermatogenesis, have been shown to evolve at a faster rate relative to genes associated with other functions and tissues. These survey studies usually group a wide variety of genes with different characteristics and evolutionary histories as reproductive genes based on their site of expression or function. We have examined the molecular evolution of the ADAM (a disintegrin and metalloprotease) gene family, a structurally and functionally diverse group of genes expressed in reproductive and somatic tissue to test whether a variety of protein characteristics such as phylogenetic clusters, tissue of expression, and proteolytic and adhesive function can group fast evolving ADAM genes. We found that all genes were evolving under purifying selection (d(N)/d(S) < 1), although reproductive ADAMs, including those implicated in fertilization and spermatogenesis, evolved at the fastest rate. Genes with a role in binding to cell receptors in endogenous tissue appear to be evolving under purifying selection, regardless of the tissue of expression. In contrast, positive selection of codon sites in the disintegrin/cysteine-rich adhesion domains was detected exclusively in ADAMs 2 and 32, two genes expressed in the testis with a potential role in sperm-egg adhesion. Positive selection was detected in the transmembrane/cytosolic tail region of ADAM genes expressed in a variety of tissues.
Self-aligned contact schemes for source-drains in submicron devices (1987)

This paper reviews the basic limitations in source-drain parasitics and source-drain contacts as devices are scaled to the submicron regime. The major portion of the paper reviews the various proposals to provide local interconnect layers which interface with the source-drain and from which all contact windows to metal-1 are made over field oxide. Among the promising approaches are HPSAC, TiN local interconnect, BOMOS and UPMOS. Significant improvements in parasitic reduction, layout density, and reliability can be achieved.