gebhart/patrepeval huggingface dataset:
Memory Model = Instruction Reordering + Store Atomicity (2006)

We present a novel framework for defining memory models in terms of two properties: thread-local Instruction Reordering axioms and Store Atomicity, which describes inter-thread communication via memory. Most memory models have the store atomicity property, and it is this property that is enforced by cache coherence protocols. A memory model with Store Atomicity is serializable; there is a unique global interleaving of all operations which respects the reordering rules. Our framework uses partially ordered execution graphs; one graph represents many instruction interleavings with identical behaviors. The major contribution of this framework is a procedure for enumerating program behaviors in any memory model with Store Atomicity. Using this framework, we show that address aliasing speculation introduces new program behaviors; we argue that these new behaviors should be permitted by the memory model specification. We also show how to extend our model to capture the behavior of non-atomic memory models such as SPARC R TSO.
A mutation in Arabidopsis that leads to constitutive expression of systemic acquired resistance. (1994)

Systemic acquired resistance (SAR) is a nonspecific defense response in plants that is associated with an increase in the endogenous level of salicylic acid (SA) and elevated expression of pathogenesis-related (PR) genes. To identify mutants involved in the regulation of PR genes and the onset of SAR, we transformed Arabidopsis with a reporter gene containing the promoter of a beta-1,3-glucanase-encoding PR gene (BGL2) and the coding region of beta-glucuronidase (GUS). The resulting transgenic line (BGL2-GUS) was mutagenized, and the M2 progeny were scored for constitutive GUS activity. We report the characterization of one mutant, cpr1 (constitutive expressor of PR genes), that was identified in this screen and shown by RNA gel blot analysis also to have elevated expression of the endogenous PR genes BGL2, PR-1, and PR-5. Genetic analyses indicated that the phenotype conferred by cpr1 is caused by a single, recessive nuclear mutation and is suppressed in plants producing a bacterial salicylate hydroxylase, which inactivates SA. Furthermore, biochemical analysis showed that the endogenous level of SA is elevated in the mutant. Finally, the cpr1 plants were found to be resistant to the fungal pathogen Peronospora parasitica NOCO2 and the bacterial pathogen Pseudomonas syringae pv maculicola ES4326, which are virulent in wild-type BGL2-GUS plants. Because the cpr1 mutation is recessive and associated with an elevated endogenous level of SA, we propose that the CPR1 gene product acts upstream of SA as a negative regulator of SAR.
Specific chromosomal imbalances in human papillomavirus-transfected cells during progression toward immortality (1997)

High risk human papillomaviruses (HPVs) known to be closely associated with cervical cancer, such as HPV16 and HPV18, have the potential to immortalize human epithelial cells in culture. Four lines of HPV-transfected keratinocytes were analyzed by comparative genomic hybridization at different time points after transfection. A number of chromosomal imbalances was found to be highly characteristic for the cultures progressing toward immortality. Whereas several of these were new and previously not found as recurrent aberrations in cervical tumors, some were identical to chromosomal changes observed during cervical carcinogenesis. The data put new emphasis on the studied cell system as a relevant model for HPV-induced pathogenesis.
Beyond Traditional Cross Couplings: The Scope of the Cross Dehydrogenative Coupling Reaction (2010)

The development of new and environmentally compatible methods for the synthesis of C-C and C-heteroatom bonds is of great significance to researchers. The cross dehydrogenative coupling (CDC) is emerging as an important tool for chemists with a variety of, often inexpensive, metal catalysts able to perform these reactions both regio- and enantioselectively. Perhaps more importantly CDC methodology has been shown to be extremely environmentally friendly and facile being able to be carried out in aqueous environments under an atmosphere of air. This Focus Review intends to give an overview of the most contemporary developments in this exciting and emerging area of cross-coupling chemistry.
Acute and Longer-Term Outcomes in Depressed Outpatients Requiring One or Several Treatment Steps: A STAR*D Report (2006)

When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed.
Age-Related Hyperkyphosis: Its Causes, Consequences, and Management (2010)

Diagnosis/prognosis/therapy, level 5.J Orthop Sports Phys Ther 2010;40(6):352-360, Epub 15 April 2010. doi:10.2519/jospt.2010.3099.
The Hepatitis C Virus (HCV) NS4B RNA Binding Inhibitor Clemizole Is Highly Synergistic with HCV Protease Inhibitors (2010)

Clemizole can yield high-level synergy with the protease inhibitor class. Inclusion of clemizole in future anti-HCV cocktails can represent an attractive paradigm for increasing current virologic response rates.
The Population Genetics of Using Homing Endonuclease Genes in Vector and Pest Management (2008)

Homing endonuclease genes (HEGs) encode proteins that in the heterozygous state cause double-strand breaks in the homologous chromosome at the precise position opposite the HEG. If the double-strand break is repaired using the homologous chromosome, the HEG becomes homozygous, and this represents a powerful genetic drive mechanism that might be used as a tool in managing vector or pest populations. HEGs may be used to decrease population fitness to drive down population densities (possibly causing local extinction) or, in disease vectors, to knock out a gene required for pathogen transmission. The relative advantages of HEGs that target viability or fecundity, that are active in one sex or both, and whose target is expressed before or after homing are explored. The conditions under which escape mutants arise are also analyzed. A different strategy is to place HEGs on the Y chromosome that cause one or more breaks on the X chromosome and so disrupt sex ratio. This strategy can cause severe sex-ratio biases with efficiencies that depend on the details of sperm competition and zygote mortality. This strategy is probably less susceptible to escape mutants, especially when multiple X shredders are used.
Biology of Transforming Growth Factor-&#946; Signaling (2011)

Transforming growth factor (TGF)-β signaling has been implicated as an important regulator of almost all major cell behaviors, including proliferation, differentiation, cell death, and motility. Which cell responses are induced or suppressed in response to TGF-β depends on the cell type and the context in which TGF-β signaling is received. TGF-β ligands, their receptors, and intracellular Smad effectors lie in the center of TGF-β signaling. TGF-β ligands signal via receptor serine/threonine kinases that phosphorylate and activate Smad proteins as well as other signaling molecules. Smad complexes associate with chromatin and regulate transcription, defining the biological response of a cell to TGF-β stimulation. In addition, numerous factors constitute complex networks to regulate TGF-β signaling and to provide this cytokine with the ability to induce cellular context-specific cell responses. Perturbation of the network is strongly involved in various pathological situations, including cancer and fibrosis. In this review, we consider the basic machinery of TGF-β signaling and describe several factors which make up TGF-β signaling networks. We also address major TGF-β-induced cell responses involved in several physiological and pathological conditions, including cell proliferation, fibrosis, and epithelial-mesenchymal transition.
Diatom Auxospore Scales and Early Stages in Diatom Frustule Morphogenesis: Their Potential for Use in Nanotechnology (2005)

Incomplete, forming diatom cell wall components have potential uses in nanotechnology that differ from those of mature frustules. Diminutive, discoid auxospore scales, produced after sexual reproduction, could also be evaluated for their value. The structure of developing diatom valves and girdle bands is generally simple, since features such as cribra and other ornamentation have yet to be added. They are also more lightly silicified. Bullulae and honeycomb structures give strength to the final framework of some species using a minimal amount of silica. The morphogenesis of girdle bands is shown to be unidirectional in a marine centric species, forming open-ended cylinders, another potential shape for the arsenal of structures useful to nanotechnologists.
Fourier-domain low-coherence interferometry for light-scattering spectroscopy (2003)

We present a novel method for obtaining depth-resolved spectra for determining scatterer size through elastic-scattering properties. Depth resolution is achieved with a white-light source in a Michelson interferometer with the mixed signal and reference fields dispersed by a spectrograph. The spectrum is Fourier transformed to yield the axial spatial cross correlation between the signal and reference fields with near 1-microm depth resolution. Spectral information is obtained by windowing to yield the scattering amplitude as a function of wave number. The technique is demonstrated by determination of the size of polystyrene microspheres in a subsurface layer with subwavelength accuracy. Application of the technique to probing the size of cell nuclei in living epithelial tissues is discussed.
Monitoring thymidine kinase and ganciclovir-induced changes in rat malignant glioma in vivo by nuclear magnetic resonance imaging. (1998)

We have used high resolution magnetic resonance imaging to monitor malignant rat BT4C gliomas in vivo following herpes simplex virus thymidine kinase gene and ganciclovir (GCV) treatment. Twenty-six female BDIX rats were used for the study including four controls. Serial magnetic resonance imaging was performed every 72 hours to quantify tumor volume, transverse relaxation time (T2) ,and apparent diffusion constant (ADC) of water in the tumors and in the contralateral brain. GCV treatment was given twice a day, intraperitoneally, for 21 days. The gliomas exhibited low T2 and ADC values (before treatment), compared to normal brain, indicating the presence of high cell density tumors. Following GCV treatment, a regional increase in T2 and ADC was observed as early as day 4 of the treatment, even though the tumor volume was still increasing. These observations suggested evolution of local necroses which were confirmed by histology. In a group of five tumor bearing rats, retrovirus-producing packaging cell injections were given intratumorally to mimic clinically relevant gene therapy. In these cases, only small and short-lasting T2 and ADC elevations were found following GCV treatment without an effect on the overall tumor growth and outcome. Our results show that quantitative magnetic resonance imaging including T2 and ADC, is superior to robust volume measurements in predicting an early response to retrovirus-mediated gene therapy in vivo.
Amelioration of Experimental Autoimmune Uveoretinitis by Aldose Reductase Inhibition in Lewis Rats (2011)

These results suggest that AR could be a novel mediator of bovine IRBP-induced uveitis in rats.
Recall Proliferation Potential of Memory CD8+ T Cells and Antiviral Protection (2005)

Abstract Memory CD8+ T cells play a crucial role in mediating protection from infection with viruses and other intracellular pathogens. Memory T cells are not a homogenous cellular population and may be separated into central memory T cells with substantial recall proliferation capacity and effector memory T cells with limited recall proliferation capacity. It has been suggested that the protective capacity of effector memory T cells is more limited than that of central memory T cells in viral infections. Here, we show that pronounced recall proliferation potential is indeed key for protection against lymphocytic choriomeningitis virus, which replicates in central lymphoid organs and is controlled by contact-dependent lysis of infected cells. In contrast, recall proliferation competence is not sufficient for protection against vaccinia virus, which is replicating in peripheral solid organs and is controlled by cytokines. To protect against vaccinia virus, high numbers of effector-like T cells were required to be present in peripheral tissue before viral challenge. These data indicate that the protective capacity of different subpopulations of memory T cells may vary dependent on the nature and the route of the challenge infection, which must be considered in T cell-based vaccine design.
Pathogenic role of interleukin-21 in psoriasis (2009)

Comment on: Caruso R, et al. Nat Med 2009; 15:1013-5.
Consensus Report on Therapeutic Drug Monitoring of Mycophenolic Acid in Solid Organ Transplantation (2010)

With the increasing use of mycophenolic acid (MPA) in solid organ transplantation, the need for more accurate drug dosing has become evident. Personalized immunosuppressive therapy requires better strategies for avoidance of drug-related toxicity while maintaining efficacy. Few studies have assessed the clinical usefulness of therapeutic drug monitoring (TDM) of MPA in solid organ transplantation in a prospective way, and they have produced opposing results. To provide clinicians with an objective and balanced clinical interpretation of the current scientific evidence on TDM of MPA, a consensus meeting involving 47 experts from around the world was commissioned by The Transplantation Society and held in Rome on November 20 to 21, 2008. The goal of this consensus meeting was to offer information to transplant practitioners on clinically relevant pharmacokinetic characteristics of MPA, to rationalize the basis for currently advised target exposure ranges for MPA in various types of organ transplantation, and to summarize available methods for application of MPA TDM in clinical practice. Although this consensus report does not evaluate the final role of MPA TDM in transplantation, it seeks to examine the current scientific evidence for concentration-controlled dosing of MPA.
Nef-induced Alteration of the Early/Recycling Endosomal Compartment Correlates with Enhancement of HIV-1 Infectivity (2004)

human immunodeficiency virus type 1 (HIV-1) Nef interacts with the clathrin-associated AP-1 and AP-3 adaptor complexes, stabilizing their association with endosomal membranes. These findings led us to hypothesize a general impact of this viral protein on the endosomal system. Here, we have shown that Nef specifically disturbs the morphology of the early/recycling compartment, inducing a redistribution of early endosomal markers and a shortening of the tubular recycling endosomal structures. Furthermore, Nef modulates the trafficking of the transferrin receptor (TfR), the prototypical recycling surface protein, indicating that it also disturbs the function of this compartment. Nef reduces the rate of recycling of TfR to the plasma membrane, causing TfR to accumulate in early endosomes and reducing its expression at the cell surface. These effects depend on the leucine-based motif of Nef, which is required for the membrane stabilization of AP-1 and AP-3 complexes. Since we show that this motif is also required for the full infectivity of HIV-1 virions, these results indicate that the positive influence of Nef on viral infectivity may be related to its general effects on early/recycling endosomal compartments.
Correction of aberrant FGFR1 alternative RNA splicing through targeting of intronic regulatory elements (2004)

Alternative RNA splicing is now known to be pervasive throughout the genome and a target of human disease. We evaluated if targeting intronic splicing regulatory sequences with antisense oligonucleotides could be used to correct aberrant exon skipping. As a model, we targeted the intronic silencing sequence (ISS) elements flanking the alternatively spliced alpha-exon of the endogenous fibroblast growth factor receptor 1 (FGFR1) gene, which is aberrantly skipped in human glioblastoma. Antisense morpholino oligonucleotides targeting either upstream or downstream ISS elements increased alpha-exon inclusion from 10% up to 70% in vivo. The effect was dose dependent, sequence specific and reproducible in several human cell lines, but did not necessarily correlate with blocking of protein association in vitro. Simultaneous targeting of the ISS elements had no additive effect, suggesting that splicing regulation occurred through a shared mechanism. Broad applicability of this approach was demonstrated by similar targeting of the ISS elements of the human hnRNPA1 gene. The correction of FGFR1 gene splicing to >90% alpha-exon inclusion in glioblastoma cells had no discernable effect on cell growth in culture, but was associated with an increase in unstimulated caspase-3 and -7 activity. The ability to manipulate endogenously expressed mRNA variants allows exploration of their functional relevance under normal and diseased physiological states.
Vaccination of chickens with recombinant Salmonella expressing M2e and CD154 epitopes increases protection and decreases viral shedding after low pathogenic avian influenza challenge (2009)

Avian influenza (AI) is a significant public health concern and serious economic threat to the commercial poultry industry worldwide. Previous research demonstrates that antibodies against M2e confer protection against influenza challenge. Using the Red recombinase system in combination with overlapping extension PCR, we recently developed several novel attenuated Salmonella Enteritidis strains that express a protective M2e epitope in combination with a potential immune-enhancing CD154 peptide sequence on the Salmonella outer membrane protein lamB. Commercial Leghorn chicks were orally immunized (immunization dose: 10(6) to 10(8) cfu/chick) with saline (negative control) or one of the recombinant Salmonella strains [DeltaaroA M2e-CD154, DeltahtrA M2e-CD154, DeltaaroA-DeltahtrA M2e(4)-CD154] on day of hatch and 21 d posthatch. These candidate vaccine strains were evaluated for their ability to invade, colonize, and persist in tissues and elicit an M2e-specific antibody response. The vaccine candidate strain DeltaaroA M2e-CD154 exhibited significantly greater organ invasion in the liver and spleen at d 7 (P > 0.05); however, no marked differences in colonization of the cecal tonsils were observed. Vaccinated chickens exhibited significantly increased M2e-specific IgG responses, which were further enhanced by simultaneous expression of CD154 (P < 0.05). Virus neutralization assays gave neutralizing indices of 6.6, 6.3, and 6.3 for DeltaaroA M2e-CD154, DeltahtrA M2e-CD154, and DeltaaroA-DeltahtrA M2e(4)-CD154 seven days post booster immunization, respectively, indicating effective neutralization of AI by serum IgG of vaccinated chickens. In a subsequent direct challenge study, specific-pathogen-free Leghorn chicks immunized with DeltaaroA-DeltahtrA M2e(4)-CD154 offered significant protection against direct challenge with low pathogenic AI H7N2, but not highly pathogenic H5N1 AI. Taken together, these data suggest that these Salmonella-vectored vaccines expressing M2e in association with CD154 are effective at protecting chickens against low pathogenic AI.
Theory of epsilon-near-zero modes in ultrathin films (2015)

The physics of the epsilon-near-zero (ENZ) mode, which is supported by a nanolayer at the frequency where the dielectric permittivity vanishes, has recently been a subject of debate. In this Rapid Communication, we thoroughly investigate and clarify the physics of this mode, providing its main characteristics and its domain of existence. This understanding will benefit all the applications that rely on ENZ modes in semiconductor nanolayers, including directional perfect absorption, voltage-tunable devices, and ultrafast thermal emission.
Myocarditis-inducing epitope of myosin binds constitutively and stably to I-Ak on antigen-presenting cells in the heart. (1995)

Immune interactions in the heart were studied using a murine model of myosin-induced autoimmune myocarditis. A T cell hybridoma specific for mouse cardiac myosin was generated from A/J mice and used to demonstrate that endogenous myosin/I-Ak complexes are constitutively expressed on antigen-presenting cells in the heart. This T cell hybridoma, Seu.5, was used as a functional probe to identify a myocarditis-inducing epitope of cardiac myosin. Overlapping peptides based on the cardiac myosin heavy chain alpha (myhc alpha) sequences were synthesized and tested for their ability to stimulate Seu.5 T cells. One peptide, myhc alpha (325-357) strongly stimulated the Seu.5 T cells, localizing the epitope to this region of the myhc alpha molecule. Using truncated peptides, the epitope was further localized to residues 334-352. The myhc alpha (334-352) peptide strongly induced myocarditis when administered to A/J mice, which was histologically indistinguishable from that induced by myosin. The myhc alpha (334-352) epitope was present in cardiac myosin and not skeletal muscle myosins, providing a biochemical basis for the cardiac specificity of this autoimmune disease. Induction of myocarditis by this epitope was restricted to the myhc alpha isoform and not the myhc beta isoform, suggesting there may be a difference in the efficiency of generating tolerance to these isoforms of cardiac myosin, which are differentially developmentally regulated. The myhc alpha (334-352) epitope bound to purified I-Ak molecules in a similar manner to other I-Ak-restricted immunogenic epitopes, HEL(48-61) and RNase(43-56). Importantly, the myhc alpha (334-352) epitope was able to bind to I-Ak molecules on the surface of antigen-presenting cells in a stable manner. These findings demonstrate that autoantigenic epitopes can behave in a dominant manner and constitutively bind to class II molecules in the target organ in a similar manner to foreign immunogenic epitopes.
Information agents for automated browsing (1996)

Article Free Access Share on Information agents for automated browsing Authors: Chanda Dharap Philips Research Labs. Philips Research Labs.View Profile , Martin Freeman Philips Research Labs. Philips Research Labs.View Profile Authors Info & Claims CIKM '96: Proceedings of the fifth international conference on Information and knowledge managementNovember 1996 Pages 296–305https://doi.org/10.1145/238355.238563Published:12 November 1996Publication History 10citation496DownloadsMetricsTotal Citations10Total Downloads496Last 12 Months3Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Identification of an isoform with an extremely large Cys‐rich region of PC6, a Kex2‐like processing endoprotease (1993)

In the previous study [1993, J. Biochem. (Tokyo) 113, 132‐135] we identified PC6, a member of the Kex2 family of processing endoproteases. In this study, we identified another cDNA encoding an isoform of PC6, and designated it as PC6B and redesignated the originally identified PC6 as PC6A. PC6B had a very large Cys‐rich region consisting of 22‐times repeats of a Cys‐rich motif, and a putative transmembrane domain which is not present in PC6A. A PC6B transcript was found mainly in the intestine, while PC6A transcripts were in various tissues. These results suggest distinct roles of PC6A and PC6B in endoproteolytic processing of precursor proteins.