gebhart/patrepeval huggingface dataset:
TCP: tag correlating prefetchers (2003)

Although caches for decades have been the backbone of the memory system, the speed gap between CPU and main memory suggests their augmentation with prefetching mechanisms. Recently, sophisticated hardware correlating prefetching mechanisms have been proposed, in some cases coupled with some form of dead-block prediction. In many proposals, however correlating prefetchers demand a significant investment in hardware. In this paper we show that correlating prefetchers that work with tags instead of cache-line addresses are significantly more resource-efficient, providing equal or better performance than previous proposals. We support this claim by showing that per-set tag sequences exhibit highly repetitive patterns both within a set and across different sets. Because a single tag sequence can capture multiple address sequences spread over different cache sets, significant space savings can be achieved. We propose a tag-based prefetcher called a tag correlating prefetcher (TCP). Even with very small history tables, TCP outperforms address-based correlating prefetchers many times larger. In addition, we show that such a prefetcher can yield most of its performance benefits if placed at the L2 level of an aggressive out-of-order processor. Only if one wants prefetching all the way up to L1, is dead-block prediction required. Finally, we draw parallels between the two-level structure of TCP and similar structures for branch prediction mechanisms; these parallels raise interesting opportunities for improving correlating memory prefetchers by harnessing lessons already learned for correlating branch predictors.
Androgen and epidermal growth factor down-regulate cyclin-dependent kinase inhibitor p27Kip1 and costimulate proliferation of MDA PCa 2a and MDA PCa 2b prostate cancer cells. (1999)

Low levels of p27Kip1 in primary prostate cancer specimens have been shown to be associated with higher rates of disease recurrence and poor rates of disease-free survival in patients with localized disease. In this study, we provide the first direct evidence showing that dihydrotestosterone (DHT), a major proliferation regulator of prostate cancer, can down-regulate p27Kip1 and stimulate cyclin-dependent kinase-2 (CDK2) activity in established prostate cancer cell lines. We investigated the cooperative effects of DHT and epidermal growth factor (EGF) on the proliferation of androgen-responsive MDA PCa 2a and MDA PCa 2b prostate cancer cells. DHT and EGF each stimulated proliferation of these cells, but exposure of the cells to DHT and EGF together stimulated greater proliferation. Stimulation of cell proliferation by DHT and/or EGF was associated with increased CDK2 activity and a decreased level of p27Kip1. There seems to be a positive feedback stimulation loop between androgen-induced gene transcription and EGF-stimulated signal transduction, as one could stimulate the synthesis of the receptors for the other. Dual blockade of androgen receptor function with the antiandrogen hydroxyflutamide and EGF receptor superfamily-mediated signal transduction with the anti-EGF receptor monoclonal antibody C225 and the anti-HER2 receptor monoclonal antibody Herceptin significantly enhanced growth inhibition of the MDA PCa 2a cells. Our results demonstrate the importance of counteracting both androgen receptors and EGF receptors in the development of novel therapies for prostate cancer.
Control flow analysis (1970)

Any static, global analysis of the expression and data relationships in a program requires a knowledge of the control flow of the program. Since one of the primary reasons for doing such a global analysis in a compiler is to produce optimized programs, control flow analysis has been embedded in many compilers and has been described in several papers. An early paper by Prosser [5] described the use of Boolean matrices (or, more particularly, connectivity matrices) in flow analysis. The use of “dominance” relationships in flow analysis was first introduced by Prosser and much expanded by Lowry and Medlock [6]. References [6,8,9] describe compilers which use various forms of control flow analysis for optimization. Some recent developments in the area are reported in [4] and in [7]. The underlying motivation in all the different types of control flow analysis is the need to codify the flow relationships in the program. The codification may be in connectivity matrices, in predecessor-successor tables, in dominance lists, etc. Whatever the form, the purpose is to facilitate determining what the flow relationships are; in other words to facilitate answering such questions as: is this an inner loop?, if an expression is removed from the loop where can it be correctly and profitably placed?, which variable definitions can affect this use? In this paper the basic control flow relationships are expressed in a directed graph. Various graph constructs are then found and shown to codify interesting global relationships.
Ku Regulates the Non-Homologous End Joining Pathway Choice of DNA Double-Strand Break Repair in Human Somatic Cells (2010)

The repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genomic integrity and viability for all organisms. Mammals have evolved at least two genetically discrete ways to mediate DNA DSB repair: homologous recombination (HR) and non-homologous end joining (NHEJ). In mammalian cells, most DSBs are preferentially repaired by NHEJ. Recent work has demonstrated that NHEJ consists of at least two sub-pathways-the main Ku heterodimer-dependent or "classic" NHEJ (C-NHEJ) pathway and an "alternative" NHEJ (A-NHEJ) pathway, which usually generates microhomology-mediated signatures at repair junctions. In our study, recombinant adeno-associated virus knockout vectors were utilized to construct a series of isogenic human somatic cell lines deficient in the core C-NHEJ factors (Ku, DNA-PK(cs), XLF, and LIGIV), and the resulting cell lines were characterized for their ability to carry out DNA DSB repair. The absence of DNA-PK(cs), XLF, or LIGIV resulted in cell lines that were profoundly impaired in DNA DSB repair activity. Unexpectedly, Ku86-null cells showed wild-type levels of DNA DSB repair activity that was dominated by microhomology joining events indicative of A-NHEJ. Importantly, A-NHEJ DNA DSB repair activity could also be efficiently de-repressed in LIGIV-null and DNA-PK(cs)-null cells by subsequently reducing the level of Ku70. These studies demonstrate that in human cells C-NHEJ is the major DNA DSB repair pathway and they show that Ku is the critical C-NHEJ factor that regulates DNA NHEJ DSB pathway choice.
A Possible New Partner for Telomerase (1998)

Cell biologists have discovered what may be a key switch in the control of cellular aging. In most tissues, the telomeres, repetitive DNA sequences that cap the ends of chromosomes, shorten each time the cell divides, until the chromosomes are so frayed that the cell becomes senescent. But in a few normal cells, including those that make eggs and sperm, and in cancer cells, an enzyme called telomerase rebuilds the telomeres after each division, keeping the cell immortal. Now researchers have found a second enzyme that may enable telomerase to do its work.
Dielectric enhancement due to electrochemical double layer: Thin double layer approximation (1982)

The dielectric constant and conductivity of a dilute ensemble of immobile, spherical particles with fixed surface (zeta) potential Φo, immersed in an electrolytic solution, is obtained in the thin double layer approximation δ≪a, δ being the thickness of the double layer, and a the radius of the particles. Equations of motion for coions and counter-ions are solved by the method of matched asymptotics. The equations of motions, linearized in the applied electric field Eo and with coefficients that are functions of the unperturbed potential (zeroth order in Eo), are solved to second order in (δ/a). The term giving enhancement in the real part of the effective dielectric constant of the ensemble ε1e, is second order in δ/a; but the series converges if (δ/a)t2/(1–t2)≪1, where t=tanh(eΦo/kBT), e being the ionic charge, kB the Boltzmann constant, and T the absolute temperature. The static value of ε1e, to this order, is ε1e∼36fε1t2/(1–t2)2, where f is the volume fraction of particles, ε1 the real part of the dielectric constant of the solution. When Φo→∞, therefore, t→1, ε1e diverges as ε1e∼9/4fε′ exp(eΦo/kBT). The present treatment is free from the approximations of previous analytical results. When applicable, the theory agrees well with experiments over three decades in frequency, with one adjustable parameter Φo. Comparison with other theories are made.
Molecular cloning and characterization of mutant and wild-type human beta-actin genes. (1984)

There are more than 20 beta-actin-specific sequences in the human genome, many of which are pseudogenes. To facilitate the isolation of potentially functional beta-actin genes, we used the new method of B. Seed (Nucleic Acids Res. 11:2427-2446, 1983) for selecting genomic clones by homologous recombination. A derivative of the pi VX miniplasmid, pi AN7 beta 1, was constructed by insertion of the 600-base-pair 3' untranslated region of the beta-actin mRNA expressed in human fibroblasts. Five clones containing beta-actin sequences were selected from an amplified human fetal gene library by homologous recombination between library phage and the miniplasmid. One of these clones contained a complete beta-actin gene with a coding sequence identical to that determined for the mRNA of human fibroblasts. A DNA fragment consisting of mostly intervening sequences from this gene was then used to identify 13 independent recombinant copies of the analogous gene from two specially constructed gene libraries, each containing one of the two types of mutant beta-actin genes found in a line of neoplastic human fibroblasts. The amino acid and nucleotide sequences encoded by the unmutated gene predict that a guanine-to-adenine transition is responsible for the glycine-to-aspartic acid mutation at codon 244 and would also result in the loss of a HaeIII site. Detection of this HaeIII polymorphism among the fibroblast-derived clones verified the identity of the beta-actin gene expressed in human fibroblasts.
Use of Designed Peptide Linkers and Recombinant Hemoglobin Mutants for Drug Delivery: In VitroRelease of an Angiotensin II Analog and Kinetic Modeling of Delivery (1997)

We have designed and tested specific peptide linkers for the glutathione-mediated reductive release of the angiotensin II analog N-acetyl-CGDKVYIHPF attached to recombinant human hemoglobin mutants by a disulfide bond. Inclusion of negatively charged residues decreased the rate of release by as much as 5-fold for the N-terminal linker DCD when compared to that of the control linker CG. Two different surface cysteine mutants in the second domain of the alpha,alpha-chain of recombinant human hemoglobin, D75C and K16C, were examined for their effect on the release of peptide by reduced glutathione. The reaction of the D75C-peptide conjugate with glutathione for release of the peptide is slow, with a second-order rate constant of 2.1 M-1 S-1, allowing the possibility of long term delivery. The rate of peptide release from the K16C vs the D75C mutant was decreased 15-fold. Thus, different peptide release rates can be obtained by changing both peptide linker residues and the surface location of peptide attachment. Kinetic modeling of this release using either measured or literature values for different parameters suggests boundary conditions for application to the in vivo release of peptidomimetics, small molecules, or other drugs bound to the hemoglobin surface.
Ultraviolet B‐induced alterations of the skin barrier and epidermal calcium gradient (2007)

Ultraviolet irradiation induces a variety of cutaneous changes, including epidermal permeability barrier disruption. In the present study, we assessed the effects of ultraviolet B (UVB) irradiation in epidermal barrier function and calcium distribution in murine epidermis. Adult hairless mice were exposed to a single dose of UVB (0.15 J/cm(2)). Barrier function was evaluated by transepidermal water loss (TEWL), lanthanum perfusion. The morphological alterations were examined by histology, immunohistochemistry and electron microscopy using ruthenium tetroxide (RuO(4)) postfixation. For evaluation of the effect on epidermal calcium distribution, the ion-capture cytochemistry was employed. UVB irradiation caused a significant increase in TEWL, which peaked at day 4. In parallel, the increased number of sunburn cells and the changes in epidermal hyperplasia and proliferation were observed. Electron microscopic observation demonstrated that the water-soluble lanthanum tracer was present in the extracellular stratum corneum domains, and the increased intercellular permeability was correlated with defective organization of the extracellular lipid lamellar bilayers of the stratum corneum. Moreover, UVB irradiation also caused an appearance of calcium precipitates in the stratum corneum and transitional cell layers as well as the increased cytosolic calcium in the lower epidermis, reflecting the alterations of the epidermal calcium gradient. These results suggest that the changes of the epidermal calcium distribution pattern may correlate with the perturbation of the epidermal barrier induced by UVB irradiation.
A pharmacological study on pegylated asparaginase used in front-line treatment of children with acute lymphoblastic leukemia. (2006)

PEG-ASP given as a first-line ASP product in the context of an intensive chemotherapy protocol for pediatric ALL allowed adequate plasma enzymatic activity and asparagine depletion during both exposures to the drug. However, CSF asparagine depletion was inadequate.
The protein tyrosine kinase p56lck regulates cell adhesion mediated by CD4 and major histocompatibility complex class II proteins. (1994)

The CD4 protein is expressed on a subset of human T lymphocytes that recognize antigen in the context of major histocompatibility complex (MHC) class II molecules. Using Chinese hamster ovary (CHO) cells expressing human CD4, we have previously demonstrated that the CD4 protein can mediate cell adhesion by direct interaction with MHC class II molecules. In T lymphocytes, CD4 can also function as a signaling molecule, presumably through its intracellular association with p56lck, a member of the src family of protein tyrosine kinases. In the present report, we show that p56lck can affect cell adhesion mediated by CD4 and MHC class II molecules. The expression of wild-type p56lck in CHO-CD4 cells augments the binding of MHC class II+ B cells, whereas the expression of a mutant p56lck protein with elevated tyrosine kinase activity results in decreased binding of MHC class II+ B cells. Using site-specific mutants of p56lck, we demonstrate that the both the enzymatic activity of p56lck and its association with CD4 are required for this effect on CD4/MHC class II adhesion. Further, the binding of MHC class II+ B cells induces CD4 at the cell surface to become organized into structures resembling adhesions-type junctions. Both wild-type and mutant forms of p56lck influence CD4-mediated adhesion by regulating the formation of these structures. The wild-type lck protein enhances CD4/MHC class II adhesion by augmenting the formation of CD4-associated adherens junctions whereas the elevated tyrosine kinase activity of the mutant p56lck decreases CD4-mediated cell adhesion by preventing the formation of these structures.
Patterned Radial GaAs Nanopillar Solar Cells (2011)

Photovoltaic devices using GaAs nanopillar radial p-n junctions are demonstrated by means of catalyst-free selective-area metal-organic chemical vapor deposition. Dense, large-area, lithographically defined vertical arrays of nanowires with uniform spacing and dimensions allow for power conversion efficiencies for this material system of 2.54% (AM 1.5 G) and high rectification ratio of 213 (at ±1 V). The absence of metal catalyst contamination results in leakage currents of ∼236 nA at -1 V. High-resolution scanning photocurrent microscopy measurements reveal the independent functioning of each nanowire in the array with an individual peak photocurrent of ∼1 nA at 544 nm. External quantum efficiency shows that the photocarrier extraction highly depends on the degenerately doped transparent contact oxide. Two different top electrode schemes are adopted and characterized in terms of Hall, sheet resistance, and optical transmittance measurements.
Evidence that antipsychotic drugs are inverse agonists at D2 dopamine receptors (1997)

1. The effects of a number of D2-like dopamine receptor antagonists have been determined on forskolin-stimulated cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing the human D2short dopamine receptor (CHO-D2S cells). 2. Dopamine inhibited the effect of forskolin (as expected for a D2 receptor). However, all of the antagonists tested, apart from UH232 and (-)-butaclamol, were able to increase cyclic AMP accumulation above the forskolin control level. (+)-Butaclamol elicited a similar stimulation of forskolin-stimulated cyclic AMP accumulation in a CHO cell line expressing human D2long dopamine receptors whereas it exhibited no stimulating effect on forskolin-stimulated cyclic AMP accumulation in untransfected CHO-K1 cells. 3. There was a strong correlation between the EC50 values of these compounds for potentiation of cyclic AMP accumulation and their Ki values from radioligand binding experiments in CHO-D2S cells. 4. The effects of both (+)-butaclamol and dopamine in CHO-D2S cells were inhibited by pre-treatment with pertussis toxin indicating a role for Gi/Go proteins. 5. UH232 did not significantly affect forskolin-stimulated cyclic AMP accumulation but this substance was able to inhibit the effects of both dopamine and (+)-butaclamol in a concentration-dependent manner. Thus the effects of (+)-butaclamol on forskolin-stimulated cyclic AMP accumulation are mediated directly via the D2 receptor rather than by reversal of the effects of an endogenous agonist. 6. These data suggest that the D2 dopamine receptor antagonists tested here, many of which are used clinically as antipsychotic drugs, are in fact inverse agonists at human D2 dopamine receptors.
ChemInform Abstract: Eleven Newly Characterized Xyloglucan Oligoglycosyl Alditols: The Specific Effects of Sidechain Structure and Location on 1H NMR Chemical Shifts. (1995)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Selective medium for isolation and enumeration of Bifidobacterium spp (1988)

A new method was developed for the isolation and enumeration of Bifidobacterium spp. from natural aquatic environments. The method was based on the utilization of a new medium, Bifidobacterium iodoacetate medium 25, and resuscitation techniques were used to isolate injured bifidobacteria. The new medium was tested with a nonselective reference medium on sewage and sewage-polluted surface waters. Relatively little colonial growth of any other bacterial genera occurred; when such colonies did grow, Bifidobacterium could be easily differentiated by its colonial morphology or, after Gram staining, by its typical bifidobacterial morphology.
Enterococcal colonization of the gastro-intestinal tract: role of biofilm and environmental oligosaccharides (2006)

The biofilm-positive phenotype of the wild-type strain seems to be associated with colonization of enterococci in the gut and the presence of oligosaccharides in food may influence biofilm formation and therefore colonization of enterococci in the gastrointestinal system.
Organosilicon chemistry. Part 21. Reactions of NN-bistrifluoromethylamino-oxyl and perfluoro(2,4-dimethyl-3-oxa-2,4-diazapentane) with vinylsilanes, and pyrolysis of the resulting adducts (1978)

The oxyl (CF3)2N·O˙ and the oxadiazapentane (CF3)2N·O·N(CF3)2 on reaction with the vinylsilanes CH2:CH·SiX3, CH2:CCl·SiX3, and CHCl:CH·SiX3 give the corresponding adducts in high yield; with the silane cis-MeCH:CH·SiCl3 reaction with the diazapentane affords the 1 : 1 adduct (50%) and the allylic substitution product (CF3)2N·O·CH2·CH:CH·SiCl3(50%). The adducts on thermolysis generally rearrange, e.g. RCH2·CH(SiX3)·O·N(CF3)2→RCH2·CH(O·SiX3)·N(CF3)2[R =(CF3)2N·O or (CF3)2N], but those containing two or three fluorine substituents on silicon, and/or chlorine in the alkyl group, undergo elimination reactions. Three different modes of elimination can occur involving: (i) nucleophilic attack by fluorine in the α-(CF3)2N·O group on silicon to eliminate a fluorosilane and perfluoro-2-azapropene and form a carbonyl compound, e.g.(CF3)2N·O·CH2·CH(SiF3)·O·N(CF3)2→ SiF4+ CF3N:CF2+(CF3)2N·CH2·CHO; (ii) nucleophilic attack by an α-chlorine atom on silicon to eliminate a chlorosilane and form an amide, e.g.(CF3)2N·CH2·CCl(SiCl3)·O·N(CF3)2→ SiCl4+(CF3)2N·CH2·CO·N(CF3)2; and (iii) intramolecular elimination of bis(trifluoromethyl)amine followed by intermolecular elimination of hexafluorodisilane and chloroketen to give an ester, i.e.(CF3)2N·O·CHCl·CH(SiF3)·O·N(CF3)2→(CF3)2NH +(CF3)2N·O·CHCl·CO·SiF3 followed by 2(CF3)2N·O·CHCl·CO·SiF3→ Si2F6+ CHCl:C:O +(CF3)2N·O·CHCl·CO2·N(CF3)2.
Molecular characterization of binding subcomponents of Clostridium botulinum type C progenitor toxin for intestinal epithelial cells and erythrocytes (2004)

Clostridium botulinum type C 16S progenitor toxin consists of a neurotoxin (NTX), a non-toxic non-HA (NTNH), and a haemagglutinin (HA). The HA acts as an adhesin, allowing the 16S toxin to bind to intestinal epithelial cells and erythrocytes. In type C, these bindings are dependent on sialic acid. The HA consists of four distinct subcomponents designated HA1, HA2, HA3a and HA3b. To identify the binding subcomponent(s) of HA of type C 16S toxin, all of the HA-subcomponents and some of their precursor forms were produced as recombinant proteins fused to glutathione S-transferase (GST). These proteins were evaluated for their capacity to adhere to intestinal epithelial cells of guinea pig and human erythrocytes. GST-HA1, GST-HA3b and GST-HA3 (a precursor form of HA3a and HA3b) bound intestinal epithelial cells and erythrocytes, whereas GST alone, GST-HA2 and GST-HA3a did not. GST-HA3b and GST-HA3 showed neuraminidase-sensitive binding to the intestinal epithelial cells and erythrocytes, whereas GST-HA1 showed neuraminidase-insensitive binding. TLC binding assay revealed that GST-HA3b and GST-HA3 recognized sialosylparagloboside (SPG) and GM3 in the ganglioside fraction of the erythrocytes, like native type C 16S toxin [Inoue, K. et al. (1999). Microbiology 145, 2533-2542]. On the other hand, GST-HA1 recognized paragloboside (PG; an asialo- derivative of SPG) in addition to SPG and GM3. Deletion mutant analyses of GST-HA3b showed that the C-terminal region of HA3b is important for its binding activity. Based on these data, it is concluded that the HA component contains two distinct carbohydrate-binding subcomponents, HA1 and HA3b, which recognize carbohydrates in different specificities.
Methoxyindoles and Photoreceptor Metabolism: Activation of Rod Shedding (1983)

Using an in vitro eye-cup preparation, we have evaluated a potential relationship between methoxyindole metabolism and photoreceptor disk shedding. Melatonin, 6-chloromelatonin, and 5-methoxytryptophol all activate rod disk shedding in culture. The effect is compound specific since serotonin and N-acetylserotonin are without effect, and it is similar to shedding in vivo because it is evoked by light and is quantitatively comparable to a normal intact animal response. The results suggest the involvement of 5-methoxyindoles in the control of rhythmic photoreceptor metabolism.