gebhart/patrepeval huggingface dataset:
Multiple-block ahead branch predictors (1996)

A basic rule in computer architecture is that a processor cannot execute an application faster than it fetches its instructions. This paper presents a novel cost-effective mechanism called the two-block ahead branch predictor. Information from the current instruction block is not used for predicting the address of the next instruction block, but rather for predicting the block following the next instruction block.This approach overcomes the instruction fetch bottle-neck exhibited by wide-dispatch "brainiac" processors by enabling them to efficiently predict addresses of two instruction blocks in a single cycle. Furthermore, pipelining the branch prediction process can also be done by means of our predictor for "speed demon" processors to achieve higher clock rate or to improve the prediction accuracy by means of bigger prediction structures.Moreover, and unlike the previously-proposed multiple predictor schemes, multiple-block ahead branch predictors can use any of the branch prediction schemes to perform the very accurate predictions required to achieve high-performance on superscalar processors.
Improvement of HSV-1 necrotizing keratitis with amniotic membrane transplantation. (2001)

AMT promotes rapid epithelialization and reduces stromal inflammation and ulceration in HSV-1 keratitis. AMT in mice with HSV necrotizing stromal keratitis appears to be a useful model for investigating the effect and the action mechanism of human amniotic membrane.
Two Photons Shine In 3-D Data Storage (1996)

RETURN TO ISSUEPREVNewsNEXTTwo Photons Shine In 3-D Data StorageOrganic dyes show promise for computer memories, cancer therapy, microscopyRON DAGANIView Author Information C&EN WashingtonCite this: Chem. Eng. News 1996, 74, 39, 68–70Publication Date (Print):September 23, 1996Publication History Published online12 November 2010Published inissue 23 September 1996https://pubs.acs.org/doi/10.1021/cen-v074n039.p068https://doi.org/10.1021/cen-v074n039.p068newsACS PublicationsCopyright © 1996 American Chemical SocietyArticle Views6Altmetric-Citations4LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options SUBJECTS:Materials,Photonics,Polymers Get e-Alerts
Transversal and Longitudinal Images from the Retina of the Living Eye Using Low Coherence Reflectometry (1998)

An optical coherence tomography (OCT) system to produce both longitudinal and transversal images of the in vivo human eye is presented. For the first time, OCT transversal images collected from the living eye at 50-μm depth steps show details unobtainable with the state-of-the-art scanning laser ophthalmoscope. Images of up to 3×3 mm are produced from the retina in less than a second. For images larger than 1.6×1.6 mm, a path modulation is introduced by the galvanometric scanning mirror and is used as an effective phase modulation method.© 1998 Society of Photo-Optical Instrumentation Engineers.
Nonpsychotropic Synthetic Cannabinoids (2000)

Unlike natural cannabinoids which belong to the 6aR - trans series, the synthetic dexanabinol (HU-211), a 6aS-trans enantiomer, does not have affinity toward cannabinoid receptors and is devoid of cannabimimetic activity. On the other hand, dexanabinol demonstrated significant neuroprotective properties which prompted its development as a therapeutic agent. We now present the extension of a series of 6aS-trans cannabinoids with novel derivatives, including water soluble derivatives and congeners of dexanabinol.
The encapsulation of a model protein in poly (D, L lactide-co-glycolide) microparticles of various sizes: an evaluation of process reproducibility (1997)

Poly (D, L lactide-co-glycolide) and poly (D, L lactide) microparticles were prepared by solvent evaporation and the process reproducibility was evaluated in terms of the loading of a model protein into the microparticles, the microparticle size and the in-vitro release profiles of the protein. The results showed that the microencapsulation method allowed the preparation of microparticles with mean sizes from < 0.5 micron to 100 microns in size, with protein entrapment from 0.5 to 5% w/w. The microparticles were smooth and free from surface defects. Moreover, the reproducibility of the preparation method was demonstrated by the in-vitro release profiles obtained using different batches of microparticles prepared under similar conditions and by the reproducibility of microparticle size and protein loading. The results demonstrated that the preparation method was both robust and reproducible and allowed the preparation of microparticles with desired characteristics in terms of loading levels, particle size and release rates.
Isolation and characterization of the Escherichia coli msbB gene, a multicopy suppressor of null mutations in the high-temperature requirement gene htrB (1992)

Previous work established that the htrB gene of Escherichia coli is required for growth in rich media at temperatures above 32.5 degrees C but not at lower temperatures. In an effort to determine the functional role of the htrB gene product, we have isolated a multicopy suppressor of htrB, called msbB. The msbB gene has been mapped to 40.5 min on the E. coli genetic map, in a 12- to 15-kb gap of the genomic library made by Kohara et al. (Y. Kohara, K. Akiyama, and K. Isono, Cell 50:495-508, 1987). Mapping data show that the order of genes in the region is eda-edd-zwf-pykA-msbB. The msbB gene codes for a protein of 37,410 Da whose amino acid sequence is similar to that of HtrB and, like HtrB, the protein is very basic in nature. The similarity of the HtrB and MsbB proteins could indicate that they play functionally similar roles. Mutational analysis of msbB shows that the gene is not essential for E. coli growth; however, the htrB msbB double mutant exhibits a unique morphological phenotype at 30 degrees C not seen with either of the single mutants. Analysis of both msbB and htrB mutants shows that these bacteria are resistant to four times more deoxycholate than wild-type bacteria but not to other hydrophobic substances. The addition of quaternary ammonium compounds rescues the temperature-sensitive phenotype of htrB bacteria, and this rescue is abolished by the simultaneous addition of Mg2+ or Ca2+. These results suggest that MsbB and HtrB play an important role in outer membrane structure and/or function.
Highly optimized tunable Er/sup 3+/-doped single longitudinal mode fiber ring laser, experiment and model (1993)

A continuous wave (CW) tunable diode-pumped Er/sup 3+/-doped fiber ring laser, pumped by diode laser at wavelengths around 1480 nm, is discussed. Wavelength tuning range of 42 nm, maximum slope efficiency of 48% and output power of 14.4 mW have been achieved. Single longitudinal mode lasing with a linewidth of 6 kHz has been measured. A fast model of erbium-doped fiber laser was developed and used to optimize output parameters of the laser.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Melanoma tumors frequently acquire LRP2/megalin expression, which modulates melanoma cell proliferation and survival rates (2015)

We show that the multiligand receptor megalin, known to mediate uptake and trafficking of nutrients and signaling molecules, is frequently expressed in malignant melanoma samples. Expression of megalin-encoding mRNA was investigated in 65 samples of nevi, melanomas, and melanoma metastases and was observed in more than 60% of the malignant samples, while only in 20% of the benign counterparts. Megalin expression in nevus and melanoma samples was additionally investigated by immunohistochemistry, which confirmed our mRNA-based observations. We furthermore show that a panel of tumor-derived melanoma cell lines express LRP2/megalin endogenously. In these cells, megalin is internalized from the cell surface and localizes extensively to intracellular vesicles, confirming receptor activity and pointing toward association with the endocytic apparatus. Groundbreaking, our results indicate that sustained megalin expression in melanoma cells is crucial for cell maintenance, as siRNA-mediated reduction in melanoma cell expression of LRP2/megalin significantly decreases melanoma cell proliferation and survival rates.
An important role for the activation peptide domain in controlling factor IX levels in the blood of haemophilia B mice (2005)

The factors responsible for the removal of injected factor IX (fIX) from the blood of individuals with haemophilia B are only partly understood, and may include binding to endothelial or subendothelial sites, passive extravasation related to size or charge, or interactions requiring fIX activation. To investigate these issues, we have produced and characterised recombinant fIX proteins with amino acid changes: delta155-177, an internal deletion which removes most of the activation peptide while retaining the activation cleavage sites; S365A, which inactivates the serine protease activity of fIXa; and K5A, previously shown to eliminate fIX binding of endothelial/subendothelial collagen IV. All proteins were expressed in stably transfected HEK 293 cells, purified by immunoaffinity chromatography, and compared to the wild type HEK 293-derived protein (fIX (WT)). Mutant fIX proteins K5A and delta155-177 exhibited 72 and 202% of the specific activity of fIX (WT), respectively; S365A was without activity. Following intravenous injection in haemophilia B (fIX knockout) mice, recoveries did not differ for fIX (WT) and delta155-177, but were higher for K5A and S365A. The terminal catabolic half-life of delta155-177, alone among the mutants, was increased, by 45% versus fIX (WT). Nine hours post-injection, the observed areas under the clearance curve (AUCs) of delta155-177 and K5, but not S365A, were elevated 2-fold. delta155-177 was equally effective as fIX (WT) in reducing blood loss following tail vein transection in haemophilia B mice. Our results suggest that deletion of the multiple sites of fIX post-translational modification found within the activation peptide eliminated important fIX clearance motifs.
An electroporation chip based on flexible microneedle array for in vivo nucleic acid delivery (2014)

This paper reports a flexible microneedle array (MNA) electroporation chip for in vivo nucleic acid delivery, which is of great importance for gene therapy. Silicon MNA is proposed to penetrate the high-resistant stratum corneum, while a flexible parylene substrate is used to fit the natural shape of electroporated objects. The chip provides a sufficient electrical field beneath the skin for electroporation with low voltage, which is less likely to harm tissues. Using the proposed chip, we successfully achieved plasmid DNA expression and siRNA delivery in living tissue with low voltage (30-40V). Neither physical nor biological harm to skin was observed.
Nonalcoholic Steatohepatitis (1980)

Nonalcoholic steatohepatitis is a poorly understood and hitherto unnamed liver disease that histologically mimics alcoholic hepatitis and that also may progress to cirrhosis. Described here are findings in 20 patients with nonalcoholic steatohepatitis of unknown cause. The biopsy specimens were characterized by the presence of striking fatty changes with evidence of lobular hepatitis, focal necroses with mixed inflammatory infiltrates, and, in most instances, Mallory bodies; Evidence of fibrosis was found in most specimens, and cirrhosis was diagnosed in biopsy tissue from three patients. The disease was more common in women. Most patients were moderately obese, and many had obesity-associated diseases, such as diabetes mellitus and cholelithiasis. Presence of hepatomegaly and mild abnormalities of liver function were common clinical findings. Currently, we know of no effective therapy.
Improved Resolution and Very High Sensitivity in MALDI TOF of Matrix Surfaces Made by Fast Evaporation (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImproved Resolution and Very High Sensitivity in MALDI TOF of Matrix Surfaces Made by Fast EvaporationOle. Vorm, Peter. Roepstorff, and Matthias. MannCite this: Anal. Chem. 1994, 66, 19, 3281–3287Publication Date (Print):October 1, 1994Publication History Published online1 May 2002Published inissue 1 October 1994https://pubs.acs.org/doi/10.1021/ac00091a044https://doi.org/10.1021/ac00091a044research-articleACS PublicationsRequest reuse permissionsArticle Views4054Altmetric-Citations595LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Polarity gene alterations in pure invasive micropapillary carcinomas of the breast (2014)

In our comprehensive molecular analysis of IMPC, we identified numerous genomic alterations without any recurrent fusion genes. Recurrent somatic mutations of genes participating in cellular polarity and shape suggest that they, together with other biological alterations (such as epigenetic modifications and stromal alterations), could contribute to the morphological pattern of IMPC. Though none of the individual abnormalities demonstrated specificity for IMPC, whether their combination in IMPC may have a cumulative effect that drives the abnormal polarity of IMPC needs to be examined further with in vitro experiments.
High-Dose Atorvastatin Reduces Total Plasma Levels of Oxidized Phospholipids and Immune Complexes Present on Apolipoprotein B-100 in Patients With Acute Coronary Syndromes in the MIRACL Trial (2004)

After atorvastatin treatment, total OxPL on all apoB-100 particles was decreased. However, there was enrichment of OxPL on a smaller pool of apoB-100 particles, in parallel with similar increases in Lp(a), suggesting binding by Lp(a). These data support the hypothesis that atorvastatin promotes mobilization and clearance of proinflammatory OxPL, which may contribute to a reduction in ischemic events after ACS.
Oligomerization of Wild Type and Nonfunctional Mutant Angiotensin II Type I Receptors Inhibits Gαq Protein Signaling but Not ERK Activation (2004)

The 7-transmembrane or G protein-coupled receptors relay signals from hormones and sensory stimuli to multiple signaling systems at the intracellular face of the plasma membrane including heterotrimeric G proteins, ERK1/2, and arrestins. It is an emerging concept that 7-transmembrane receptors form oligomers; however, it is not well understood which roles oligomerization plays in receptor activation of different signaling systems. To begin to address this question, we used the angiotensin II type 1 (AT(1)) receptor, a key regulator of blood pressure and fluid homeostasis that in specific context has been described to activate ERKs without activating G proteins. By using bioluminescence resonance energy transfer, we demonstrate that AT(1) receptors exist as oligomers in transfected COS-7 cells. AT(1) oligomerization was both constitutive and receptor-specific as neither agonist, antagonist, nor co-expression with three other receptors affected the bioluminescence resonance energy transfer 2 signal. Furthermore, the oligomerization occurs early in biosynthesis before surface expression, because we could control AT(1) receptor export from the endoplasmic reticulum or Golgi by using regulated secretion/aggregation technology (RPD trade mark ). Co-expression studies of wild type AT(1) and AT(1) receptor mutants, defective in either ligand binding or G protein and ERK activation, yielded an interesting result. The mutant receptors specifically exerted a dominant negative effect on Galpha(q) activation, whereas ERK activation was preserved. These data suggest that distinctly active conformations of AT(1) oligomers can couple to each of these signaling systems and imply that oligomerization plays an active role in supporting these distinctly active conformations of AT(1) receptors.
The Role of the Sulfhydryl Groups of Tropomyosin and Troponin in the Calcium Control of Actomyosin Contractility (1968)

Abstract Methods for preparing troponin and tropomyosin from ethanol-extracted muscle are presented. Examination of these proteins by disc electrophoresis indicated that the troponin preparation is homogeneous. If precautions were taken to assure that the —SH groups of tropomyosin were not permitted to oxidize during preparation or electrophoresis, tropomyosin appeared to be nearly homogeneous. Traces of troponin, however, appeared in all samples. Neither troponin nor tropomyosin was found to make actomyosin superprecipitation sensitive to the removal of Ca++. Combined, they were effective. A moderately wide range of troponin to tropomyosin ratios (between 1:1 and 3:1) were found to provide optimal sensitization of actomyosin. At a troponin to tropomyosin ratio of 1.3:1, 35 µg of this protein mixture inhibited by 85% 200 µg of actomyosin. The ability of troponin to collaborate with tropomyosin in the sensitization of actomyosin was lost to varying degrees if the troponin —SH groups were allowed to react with p-chloromercuribenzoate or N-ethylmaleimide or if the —SH groups were not protected during preparation. In contrast, the function of tropomyosin was found not to correlate with the state of its —SH groups. Troponin was found to be a potent calcium-binding substance, possessing 24 µmoles of high affinity calcium-binding sites per g. The high affinity site had an apparent affinity constant of approximately 2.4 x 106 m-1. It is hypothesized that the binding of calcium to this site inactivates troponin and that this is the mechanism whereby calcium activates myofibrillar contraction. It is concluded that tropomyosin does not possess a similar class of calcium-binding sites. The affinity of troponin for calcium was unaltered by reaction of its —SH groups. The number of high affinity calcium-binding sites was, however, doubled to approximately 40 µmoles of sites per g by reaction of troponin with —SH reagents.
Platelet-derived growth factor: roles in normal and v-sis transformed cells. (1985)

Platelet-derived growth factor (PDGF) is the most potent mitogenic protein in human serum. The normal roles of this protein may relate to its potent mitogenic properties and its activities in directed cell migration and at sites of wounds. PDGF is a heterodimeric protein of approximately 30,000 molecular weight; one polypeptide chain of PDGF is highly homologous to the predicted amino acid sequence of p28v-sis, the putative transforming protein of simian sarcoma virus (SSV), suggesting a major role of growth factor activity in transformation by SSV. PDGF-like growth promoting activity is found in SSV-transformed cells and is secreted into conditioned media where it appears to interact with PDGF cell surface receptors to stimulate 3H-thymidine incorporation into DNA of cells secreting this protein. Transformation by SSV may in part be mediated by the autocrine stimulation of cell growth by the PDGF-like mitogenic properties of the transforming protein of SSV.
Human Papillomavirus E6E7-Mediated Adenovirus Cell Killing: Selectivity of Mutant Adenovirus Replication in Organotypic Cultures of Human Keratinocytes (2001)

Replication-competent adenoviruses are being investigated as potential anticancer agents. Exclusive virus replication in cancer cells has been proposed as a safety trait to be considered in the design of oncolytic adenoviruses. From this perspective, we have investigated several adenovirus mutants for their potential to conditionally replicate and promote the killing of cells expressing human papillomavirus (HPV) E6 and E7 oncoproteins, which are present in a high percentage of anogenital cancers. For this purpose, we have employed an organotypic model of human stratified squamous epithelium derived from primary keratinocytes that have been engineered to express HPV-18 oncoproteins stably. We show that, whereas wild-type adenovirus promotes a widespread cytopathic effect in all infected cells, E1A- and E1A/E1B-deleted adenoviruses cause no deleterious effect regardless of the coexpression of HPV18 E6E7. An adenovirus deleted in the CR2 domain of E1A, necessary for binding to the pRB family of pocket proteins, shows no selectivity of replication as it efficiently kills all normal and E6E7-expressing keratinocytes. Finally, an adenovirus mutant deleted in the CR1 and CR2 domains of E1A exhibits preferential replication and cell killing in HPV E6E7-expressing cultures. We conclude that the organotypic keratinocyte culture represents a distinct model to evaluate adenovirus selectivity and that, based on this model, further modifications of the adenovirus genome are required to restrict adenovirus replication to tumor cells.
Genetic Engineering of T Cells to Target HERV-K, an Ancient Retrovirus on Melanoma (2015)

Adoptive cellular immunotherapy with HERV-K env-specific CAR(+) T cells represents a clinically appealing treatment strategy for advanced-stage melanoma and provides an approach for targeting this TAA on other solid tumors.
Revisiting the Mechanism of P450 Enzymes with the Radical Clocks Norcarane and Spiro[2,5]octane (2002)

Norcarane (1) and spiro[2.5]octane (2) yield different product distributions depending on whether they are oxidized via concerted, radical, or cationic mechanisms. For this reason, these two probes were used to investigate the mechanisms of hydrocarbon hydroxylation by two mammalian and two bacterial cytochrome P450 enzymes. Products indicative of a radical intermediate with a lifetime ranging from 16 to 52 ps were detected during the oxidation of norcarane by P450(cam) (CYP101), P450(BM3) (CYP102), CYP2B1, and CYP2E1. Trace amounts of the cation rearrangement product were observed with norcarane for all but CYP2E1, while no cation or radical rearrangement products were observed for spiro[2.5]octane. The results for the oxidation of norcarane with a radical rearrangement rate of 2 x 10(8) s(-1) are consistent with the involvement of a two-state radical rebound mechanism, while for the slower (5 x 10(7) s(-1)) spiro[2,5]oct-4-yl radical rearrangement products were beyond detection. Taken together with earlier data for the hydroxylation of bicyclo[2.1.0]pentane, which also suggested a 50 ps radical lifetime, these three structurally similar and functionally simple substrates show a consistent pattern of rearrangement that supports a radical rebound mechanism for this set of cytochrome P450 enzymes.