gebhart/patrepeval huggingface dataset:
Elevated DNA polymerase alpha, DNA polymerase beta, and DNA topoisomerase II in a melphalan-resistant rhabdomyosarcoma xenograft that is cross-resistant to nitrosoureas and topotecan. (1994)

Previous investigations have revealed that the human TE-671 MR human rhabdomyosarcoma xenograft selected in vivo for melphalan resistance (M. C. Rosenberg, et al., Cancer Res., 49: 6917-6922, 1989) is cross-resistant to a wide variety of alkylating agents and to bleomycin, but is collaterally sensitive to etoposide. Although glutathione levels were noted to be elevated in TE-671 MR compared to the melphalan-sensitive parental TE-671 xenograft, treatment with buthionine sulfoximine to deplete glutathione levels did not fully restore melphalan sensitivity in the TE-671 MR xenograft. The present studies were undertaken to search for additional mechanisms of resistance in the TE-671 MR xenograft. Drug sensitivity testing performed at the dose of agents that was lethal to 10% of the animals revealed that the TE-671 MR xenograft maintained resistance to the bifunctional cross-linking agent 1,3-bis(2-chloroethyl)-1-nitrosourea and was cross-resistant to the topoisomerase I poison topotecan. Treatment with buthionine sulfoximine did not sensitize the TE-671 MR xenograft to 1,3-bis(2-chloroethyl)-1-nitrosourea. Further, even though O6-alkylguanine-DNA alkyltransferase levels were high in both the TE-671 and TE-671 MR xenografts, depletion of O6-alkylguanine-DNA alkyltransferase activity by treatment with O6-benzylguanine substantially sensitized the TE-671 xenografts but not the TE-671 MR xenografts, suggesting an additional mechanism of resistance. Measurement of additional enzyme activities that might be involved in DNA repair revealed significant elevations in DNA polymerase alpha (46 +/- 8 (SD) units/mg protein in TE-671, 69 +/- 6 units/mg protein in TE-671 MR, P < 0.05) and DNA polymerase beta (0.43 +/- 0.01 units/mg protein in TE-671, 0.78 +/- 0.12 units/mg protein in TE-671 MR, P < 0.05) but not DNA polymerase delta or total DNA ligase. Examination of topoisomerases by activity assays and Western blotting revealed a 2-fold increase in topoisomerase II and a 2-fold decrease in topoisomerase I in the TE-671 MR xenograft compared to the parental xenograft, apparently explaining the collateral sensitivity to etoposide and cross-resistance to topotecan. These results suggest that TE-671 MR xenografts contain multiple changes in activities of DNA repair-related proteins and other nuclear proteins that could contribute to alkylating agent resistance.
Business Flexibility and Operational Efficiency - Making Trade-Offs in Service Oriented Architecture (2005)

Web service enabled Service Oriented Architecture has been an increasingly popular approach for enterprises to develop an agile and flexible architecture. However, very little guidance on the granularity of âservicesâ has been provided, which has an impact on the trade-off between flexibility and coordination effort. We suggest that the lack of granularity guidance is due to the lack of the explicit positioning of âservicesâ in the traditional enterprise architecture literature. After clarifying the relationship between âservicesâ and âprocessesâ, we provide an approach to define âprocess complexityâ along certain dimensions and use this complexity metric to decide on the appropriate granularity of the âservicesâ.
The role of baroreflex activation therapy in sympathetic modulation for the treatment of resistant hypertension (2012)

Hypertension remains a leading cause of morbidity and mortality in the world, and the prevalence of resistant and refractory hypertension continues to increase dramatically. Conditions associated with long-term poorly controlled hypertension include ischaemic heart disease, cardiomyopathy, stroke and renal failure. Pharmacologic therapy has long been the hallmark of treatment for the many patients for whom therapeutic lifestyle modifications fail. There is now a vast array of drug classes in the armamentarium, including beta-blockers, ACE inhibitors, ARBs, calcium channel blockers, to name a few. Despite the advances and addition of novel drug classes and more potent agents within the classes, a substantial proportion of patients fail to achieve the goal even with available therapies. Poly-pharmacy is wrought with side-effects and patients have psychological limits regarding how many medications they are willing to take.

Manipulation of the sympathetic system has demonstrated benefit in patients with malignant hypertension in the pre-antihypertensive medication era. Currently, two separate and distinct approaches have been revived and evaluated in new ways. Surgical sympathectomy was first attempted in the 1930s for patients with peripheral vascular disease, in an attempt to improve circulation by reducing vasoconstrictive effects of the sympathetic system. In the 1940s and 1950s, the scope of the technique was extended to patients with malignant hypertension.1–5 Unfortunately, the side-effect profile associated with surgical splanchnicectomy (eg, impotence, severe orthostatic hypotension and urinary/faecal incontinence) was significant enough that, not surprisingly, the technique fell out of favour.6

More recently, with advances in technology for percutaneous delivery of radiofrequency energy to create deep thermal injury …
Regulation of production of type 1 pili among urinary tract isolates of Escherichia coli (1986)

The piliation and hemagglutination properties of 54 consecutive Escherichia coli isolates from women with recurrent urinary tract infections were studied. Mannose-sensitive hemagglutination (MSHA) of guinea pig erythrocytes, characteristic of type 1-piliated bacteria, was produced by 75% of the isolates, 32% produced mannose-insensitive hemagglutination, and 14% produced no hemagglutination reaction. The production of type 1 pili was examined in those strains that produced MSHA only. Studies with antiserum prepared against purified pili suggested that at least three subtypes of type 1 hemagglutinins were represented among the isolates. All of the type 1-piliated isolates produced MSHA after serial subculture in static broth. After growth on agar, selected type 1-piliated isolates were subdivided into two groups. Many strains apparently suppressed piliation during growth on agar (regulated variants); all colonies became MSHA negative and were composed of nonpiliated cells as shown by electron microscopy. The loss of the MSHA phenotype often occurred after a single overnight passage on agar, and any remaining hemagglutinin was gradually lost with one to three additional passages. Seven strains, however, retained a significant hemagglutination titer after multiple subcultures on agar, and they produced colonies consisting of a mixed population of piliated and nonpiliated cells. These strains were apparently able to oscillate between states of pilus expression and nonexpression during growth on agar (random phase variants). When nonpiliated cells isolated from the mixed, random variant population were plated on agar, they gave rise to hemagglutination-positive colonies that consisted of both piliated and nonpiliated cells. The distinction between random variants and regulated variants was also observed in shaking broth cultures inoculated with nonpiliated cells. The random variants produced MSHA-positive cultures composed of piliated and nonpiliated cells, whereas the regulated strains remained nonpiliated. The results indicate that type 1 pili are a predominant adhesin of uropathogenic E. coli and that during growth on agar only about one-fourth of the type 1-piliated isolates regulate pilus expression by random phase variation.
Size-dependent propagation of Au nanoclusters through few-layer graphene (2013)

We report the size-dependent propagation of gold nanoclusters through few-layer graphene (FLG). We employ aberration-corrected scanning transmission electron microscopy (STEM) to track the fate of Au55 and Au923 clusters that have been deposited, independently and isoenergetically, onto suspended FLG films using cluster beam deposition. We demonstrate that Au55 clusters penetrate through the FLG, whereas the monodisperse Au923 clusters reside at the surface. Our approach offers a route to the controlled incorporation of dopant nanoparticles and the generation of nanoscale defects in graphene.
Interleukin 1 promotes tumor cell adhesion to cultured human endothelial cells. (1988)

We report that IL 1 acts on the endothelium, inducing a long-lasting increase in its adhesivity to tumor cells. Selective pretreatment of cultured human umbilical vein endothelial cells (EC) with IL 1 caused a significant increase in adhesion of three human colorectal carcinoma (HT-29, HCC-P2988, and HCC-M1410) cell lines and one human melanoma (A-375) cell line. Tumor necrosis factor (TNF) was as effective as IL 1 in promoting tumor cell adhesion to EC, whereas IFN gamma and IL 2 were inactive. The IL 1 and TNF induction of EC adhesivity was both concentration (threshold concentration 1 U/ml) and time dependent (peak 4-6 h), reversible within 24 h, and blocked by a protein synthesis inhibitor. The IL 1 and TNF action on EC may play a role in tumor cell lodgement.
Cancer Immunotherapy Based on Killing of Salmonella -Infected Tumor Cells (2005)

A major obstacle for the development of effective immunotherapy is the ability of tumors to escape the immune system. The possibility to kill tumor cells because they are recognized as infected rather than as malignant could help overcome immune escape mechanisms. Here we report a conceptually new approach of cancer immunotherapy based on in vivo infection of tumors and killing of infected tumor cells. Attenuated but still invasive, Salmonella typhimurium can be successfully exploited to invade melanoma cells that can present antigenic determinants of bacterial origin and become targets for anti-Salmonella-specific T cells. However, to fully appreciate the anticancer therapeutic properties of S. typhimurium, tumor-bearing mice need to be vaccinated against S. typhimurium before intratumoral Salmonella injection. Tumor infection when coupled to anti-Salmonella vaccination leads to 50% to 100% tumor-free mice with a better outcome on larger tumors. Invasive Salmonella also exert an indirect toxic effect on tumor cells through the recruitment of inflammatory cells and the cross-presentation of tumor antigens, which allow induction of tumor-specific immune response. This is effective in retarding the growth of untreated established distant tumors and in protecting the mice from subsequent tumor challenges.
Activin Decoy Receptor ActRIIB:Fc Lowers FSH and Therapeutically Restores Oocyte Yield, Prevents Oocyte Chromosome Misalignments and Spindle Aberrations, and Increases Fertility in Midlife Female SAMP8 Mice (2015)

Women of advanced maternal age (AMA) (age ≥ 35) have increased rates of infertility, miscarriages, and trisomic pregnancies. Collectively these conditions are called "egg infertility." A root cause of egg infertility is increased rates of oocyte aneuploidy with age. AMA women often have elevated endogenous FSH. Female senescence-accelerated mouse-prone-8 (SAMP8) has increased rates of oocyte spindle aberrations, diminished fertility, and rising endogenous FSH with age. We hypothesize that elevated FSH during the oocyte's FSH-responsive growth period is a cause of abnormalities in the meiotic spindle. We report that eggs from SAMP8 mice treated with equine chorionic gonadotropin (eCG) for the period of oocyte growth have increased chromosome and spindle misalignments. Activin is a molecule that raises FSH, and ActRIIB:Fc is an activin decoy receptor that binds and sequesters activin. We report that ActRIIB:Fc treatment of midlife SAMP8 mice for the duration of oocyte growth lowers FSH, prevents egg chromosome and spindle misalignments, and increases litter sizes. AMA patients can also have poor responsiveness to FSH stimulation. We report that although eCG lowers yields of viable oocytes, ActRIIB:Fc increases yields of viable oocytes. ActRIIB:Fc and eCG cotreatment markedly reduces yields of viable oocytes. These data are consistent with the hypothesis that elevated FSH contributes to egg aneuploidy, declining fertility, and poor ovarian response and that ActRIIB:Fc can prevent egg aneuploidy, increase fertility, and improve ovarian response. Future studies will continue to examine whether ActRIIB:Fc works via FSH and/or other pathways and whether ActRIIB:Fc can prevent aneuploidy, increase fertility, and improve stimulation responsiveness in AMA women.
Epidemiology, prevention, and early detection of breast cancer (2000)

Decreases in the incidence of breast cancer have not been achieved, but there is a downward trend in age-adjusted breast cancer mortality rates in the United States. Recent epidemiologic investigations continue to refine our understanding of the role of established breast cancer risk factors, such as reproductive characteristics and body mass index, and in the process advance understanding of the etiology of breast cancer. Important strides are being made in the chemoprevention of breast cancer, but clarifying the potential contributions of factors such as diet, physical activity, and cigarette smoke to the breast cancer burden is a high priority because these lifestyle behaviors also have important implications for primary prevention. The role of both environmental and endogenous exposures in breast carcinogenesis will be more clearly elucidated by studies that account for genetic polymorphisms, some of which may lead to differential susceptibility to harmful agents.
Strategic Attentive Writer for Learning Macro-Actions (2016)

We present a novel deep recurrent neural network architecture that learns to build implicit plans in an end-to-end manner purely by interacting with an environment in reinforcement learning setting. The network builds an internal plan, which is continuously updated upon observation of the next input from the environment. It can also partition this internal representation into contiguous sub-sequences by learning for how long the plan can be committed to -- i.e. followed without replaning. Combining these properties, the proposed model, dubbed STRategic Attentive Writer (STRAW) can learn high-level, temporally abstracted macro-actions of varying lengths that are solely learnt from data without any prior information. These macro-actions enable both structured exploration and economic computation. We experimentally demonstrate that STRAW delivers strong improvements on several ATARI games by employing temporally extended planning strategies (e.g. Ms. Pacman and Frostbite). It is at the same time a general algorithm that can be applied on any sequence data. To that end, we also show that when trained on text prediction task, STRAW naturally predicts frequent n-grams (instead of macro-actions), demonstrating the generality of the approach.
Consistent Streaming Through Time: A Vision for Event Stream Processing (2006)

Event processing will play an increasingly important role in constructing enterprise applications that can immediately react to business critical events. Various technologies have been proposed in recent years, such as event processing, data streams and asynchronous messaging (e.g. pub/sub). We believe these technologies share a common processing model and differ only in target workload, including query language features and consistency requirements. We argue that integrating these technologies is the next step in a natural progression. In this paper, we present an overview and discuss the foundations of CEDR, an event streaming system that embraces a temporal stream model to unify and further enrich query language features, handle imperfections in event delivery and define correctness guarantees. We describe specific contributions made so far and outline next steps in developing the CEDR system.
Genetic Code Supports Targeted Insertion of Two Amino Acids by One Codon (2009)

Strict one-to-one correspondence between codons and amino acids is thought to be an essential feature of the genetic code. However, we report that one codon can code for two different amino acids with the choice of the inserted amino acid determined by a specific 3' untranslated region structure and location of the dual-function codon within the messenger RNA (mRNA). We found that the codon UGA specifies insertion of selenocysteine and cysteine in the ciliate Euplotes crassus, that the dual use of this codon can occur even within the same gene, and that the structural arrangements of Euplotes mRNA preserve location-dependent dual function of UGA when expressed in mammalian cells. Thus, the genetic code supports the use of one codon to code for multiple amino acids.
Monoclonal antibody 12-8 recognizes a 115-kd molecule present on both unipotent and multipotent hematopoietic colony-forming cells and their precursors (1986)

A monoclonal antibody, 12-8, prepared against KG-1a cells, recognizes an approximately 115-kd cell surface antigen and reacts with 3% to 4% of bone marrow cells, including most of the blast cells. The antigen is not expressed on peripheral blood cells. Marrow cells expressing 12-8 collected by fluorescence-activated cell sorting contained nearly all of the unipotent (CFU-GM, BFU-E) and multipotent (CFU-MIX) colony-forming cells. The isolated 12-8 positive marrow population also contained precursors of these colony-forming cells. In a two-stage long-term marrow culture system employing irradiated allogeneic marrow adherent cells, 12-8 positive cells produced both unipotent and multipotent colony-forming cells for ten weeks. Moreover, the output of colony forming cells substantially exceeded the input. Antibody 12-8 appears useful for analysis and possibly enrichment of hematopoietic progenitor cells that include colony-forming cell precursors.
Atomic write FTL for robust flash file system (2005)

Flash memory is one of the essential elements for code and data storage in the mobile products. Robustness is very important in the flash memory based file system of the mobile consumer electronic devices, since sudden power failure may happen and it may cause a loss of important user data and a serious trouble which cannot be recovered by user. In this paper, we present a novel technique for a robust flash file system. This method is based on the log block FTL algorithm and guarantees that all the sectors bounded together are written completely or no sectors are written at all for any interruptions, and thus distributed metadata of flash file system can be safely updated, and the integrity of the file system can he safely maintained. Our simulation results show that the FAT file system using our method is maintained safe for sudden power failure events.
On-Chip Free-Flow Magnetophoresis:  Continuous Flow Separation of Magnetic Particles and Agglomerates (2004)

The separation of magnetic microparticles was achieved by on-chip free-flow magnetophoresis. In continuous flow, magnetic particles were deflected from the direction of laminar flow by a perpendicular magnetic field depending on their magnetic susceptibility and size and on the flow rate. Magnetic particles could thus be separated from each other and from nonmagnetic materials. Magnetic and nonmagnetic particles were introduced into a microfluidic separation chamber, and their deflection was studied under the microscope. The magnetic particles were 2.0 and 4.5 microm in diameter with magnetic susceptibilities of 1.12 x 10(-4) and 1.6 x 10(-4) m(3) kg(-1), respectively. The 4.5-microm particles with the larger susceptibility were deflected further from the direction of laminar flow than the 2.0-microm magnetic particles. Nonmagnetic 6-microm polystyrene beads, however, were not deflected at all. Furthermore, agglomerates of magnetic particles were found to be deflected to a larger extent than single magnetic particles. The applied flow rate and the strength and gradient of the applied magnetic field were the key parameters in controlling the deflection. This separation method has a wide applicability since magnetic particles are commonly used in bioanalysis as a solid support material for antigens, antibodies, DNA, and even cells. Free-flow magnetophoretic separations could be hyphenated with other microfluidic devices for reaction and analysis steps to form a micro total analysis system.
Efficient quantum computation using coherent states (2002)

We study universal quantum computation using optical coherent states. A teleportation scheme for a coherent-state qubit is developed and applied to gate operations. This scheme is shown to be robust to detection inefficiency.
Protein damage and degradation by oxygen radicals. II. Modification of amino acids. (1987)

Exposure of proteins to the hydroxyl radical (.OH) or to the combination of .OH plus the superoxide anion radical (.OH + O2-) causes gross structural modification. Such modified proteins can undergo spontaneous fragmentation or can exhibit substantial increases in proteolytic susceptibility. In the present study, with the representative protein bovine serum albumin (BSA), we report that alterations to primary structure underlie such gross structural modifications. All amino acids in BSA were susceptible to modification by both .OH and .OH + O2- +O2), although tryptophan, tyrosine, histidine, and cysteine were particularly sensitive. At a radical/BSA molar ratio (nmol of radicals/nmol of BSA) of 10, we observed an average 9-10% destruction of amino acids; whereas at a ratio of 100, the average loss was 45%. Decreasing tryptophan fluorescence provided a useful index of amino acid loss and exhibited a clear dose dependence with .OH or with .OH + O2- (+O2). Linear production of the biphenol bityrosine was observed with .OH treatment. In contrast, .OH + O2- (+O2) induced only a limited bityrosine production rate which reached an early plateau. Studies with various chemical scavengers (t-butyl alcohol, isopropyl alcohol, mannitol, urate) and gasses (N2O, N2, O2, air) revealed that .OH is the primary radical responsible for all amino acid modifications, but that O2- and O2 can further transform the products of .OH reactions. Thus, O2-/O2 can potentiate .OH-dependent destruction of many amino acids (e.g. tryptophan) while inhibiting production of bityrosine by reacting with tyrosyl (phenoxyl) radicals. No amino acid loss or bityrosine production occurred with exposure to O2- (+O2) alone. Amino acid modifications caused both by .OH alone and by .OH + O2- (+O2) progressively affected the overall electrical charge of BSA. In a pH range of 3.7-6.2, some 16 new isoelectric focusing bands were induced by .OH, and some eight new bands were induced by .OH + O2- (+O2). The alterations to primary structure observed provide the key to an understanding of the link between oxidative modification and increased proteolytic susceptibility.