gebhart/patrepeval huggingface dataset:
Aberrant Gag protein composition of a human immunodeficiency virus type 1 vif mutant produced in primary lymphocytes (1995)

Productive, spreading infection of peripheral blood lymphocytes (PBL) with human immunodeficiency virus type 1 (HIV-1) requires the viral protein Vif. To study the requirement for vif in this system, we infected PBL with a phenotypically complemented HIV-1 clone mutated in vif. Progeny virus was produced which was noninfectious in PBL but replicated in SupT1 cells. Analysis of metabolically labeled proteins of sedimentable extracellular particles made in PBL by radioimmunoprecipitation with either serum from a patient with AIDS or a monoclonal antibody reactive with HIV-1 Gag proteins revealed that vif-negative but not wild-type particles carry higher levels of p55, p41, and p38 Gag-specific proteins compared with those of p24. Similar results were obtained with sucrose-purified virions. Our data indicate that vif plays a role in Gag protein processing or in incorporation of processed Gag products into mature virions. The presence of unprocessed precursor Gag polyprotein (Pr55gag) and other Gag processing intermediates in PBL-derived vif-negative extracellular particles may contribute to the reduced infectivity of this virus.
Improving host security with system call policies (2003)

We introduce a system that eliminates the need to run programs in privileged process contexts. Using our system, programs run unprivileged but may execute certain operations with elevated privileges as determined by a configurable policy eliminating the need for suid or sgid binaries. We present the design and analysis of the &amp;quot;Systrace&amp;quot; facility which supports fine grained process confinement, intrusion detection, auditing and privilege elevation. It also facilitates the often difficult process of policy generation. With Systrace, it is possible to generate policies automatically in a training session or generate them interactively during program execution. The policies describe the desired behavior of services or user applications on a system call level and are enforced to prevent operations that are not explicitly permitted. We show that Systrace is efficient and does not impose significant performance penalties.
Gold‐Nanoshelled Microcapsules: A Theranostic Agent for Ultrasound Contrast Imaging and Photothermal Therapy (2011)

Eine wertvolle Schale: Die Kombination der elektrostatischen Abscheidung von Goldnanopartikeln auf Mikrokapseln mit der Keimbildung an Oberflächen lieferte Goldnanoschalen (siehe Bild). Dieses Nano/Mikrokomposit kann als Theranostikum sowohl für die kontrastverstärkte Ultraschallbildgebung (Diagnostikum) als auch für die Photohyperthermie (Therapeutikum) genutzt werden, was für einen Einsatz in der Photothermaltherapie bei Krebs spricht. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
3-Aryl-2-methylserines. I. A new synthesis (1968)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT3-Aryl-2-methylserines. I. A new synthesisSeemon H. Pines, Sandor Karady, and Meyer SletzingerCite this: J. Org. Chem. 1968, 33, 5, 1758–1761Publication Date (Print):May 1, 1968Publication History Published online1 May 2002Published inissue 1 May 1968https://pubs.acs.org/doi/10.1021/jo01269a012https://doi.org/10.1021/jo01269a012research-articleACS PublicationsRequest reuse permissionsArticle Views369Altmetric-Citations21LEARN 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
Inhibition of pig kidney L-aromatic amino acid decarboxylase by 2,3-methano-m-tyrosines (1992)

Both racemic (E)- and (Z)-2,3-methano-m-tyrosines (9E and 9Z) have been synthesized from a common intermediate, monoester (Z)-1-(ethoxycarbonyl)-2-[3-[(2-methoxyethoxy)methoxy]phenyl] cyclopropanecarboxylic acid (5). Quinine and ephedrine, respectively, were used to resolve their N-tert-butoxycarbonyl (Boc) derivatives. Among the compounds prepared, the (+)-(E)-diastereomer of 9 is the most potent inhibitor of L-aromatic amino acid decarboxylase (Dopa decarboxylase), having a Ki of 22 microM, with the (-)-Z-diastereomer (9Z) second at Ki = 49 microM. (+)-9E is a 45-fold more potent inhibitor of DDC than its acyclic analogue, D-m-tyrosine.
RBX1/ROC1-SCF E3 ubiquitin ligase is required for mouse embryogenesis and cancer cell survival (2009)

RBX1 (also known as ROC1) is a RING subunit of SCF (Skp1, Cullins, F-box proteins) E3 ubiquitin ligases, required for SCF to direct a timely degradation of diverse substrates, thereby regulating numerous cellular processes under both physiological and pathological conditions. Previous studies have shown that RBX1 is essential for growth in yeast, Caenorhabditis elegans and Drosophila. The role of RBX1 in mouse development and in regulation of cancer cell survival was unknown. Our recent work demonstrated that RBX1 is an essential gene for mouse embryogenesis, and targeted disruption of RBX1 causes embryonic lethality at E7.5 due to hypoproliferation as a result of p27 accumulation. We also showed that RBX1 is overexpressed in a number of human cancers, and siRNA silencing of RBX1 caused cancer cell death as a result of sequential induction of G2-M arrest, senescence and apoptosis. These findings reveal a physiological role of RBX1 during mouse development and a pathological role for the survival of human cancer cells. Differential outcomes between normal (growth arrest) and cancer cells (cell death) upon RBX1 disruption/silencing suggest RBX1 as a valid anticancer target.Comments on:Tan M, Davis SW, Saunders TL, Zhu Y, Sun Y. RBX1/ROC1 disruption results in early embryonic lethality due to proliferation failure, partially rescued by simultaneous loss of p27. Proc Natl Acad Sci USA. 2009; 106:6203-6208Jia L, Soengas MS, Sun Y. ROC1/RBX1 E3 ubiquitin ligase silencing suppresses tumor cell growth via sequential induction of G2-M arrest, apoptosis, and senescence. Cancer Res. 2009; 69:4974-82.
Double-stranded RNA-activated protein kinase mediates virus-induced apoptosis: A new role for an old actor (1999)

Eukaryotic viruses and their multicellular hosts have coevolved complex interrelationships to permit virus reproduction without destruction of the host. The IFN-induced cellular antiviral response is the first line of defense against viral infection within an animal host. On viral infection, the expression of IFN is induced at the transcriptional level. The IFN is secreted to protect adjacent cells from secondary infection, thereby limiting viral spread. Type I IFNs are composed of the different types of IFN-α that are produced in leukocytes and the IFN-β that is produced in fibroblasts and epithelial cells. Type I IFNs bind to their receptors and activate a signaling cascade that culminates in the transcriptional induction of at least 30 genes (1). Two of these genes encode latent enzymes requiring activation by binding to double-stranded (ds)RNA that is produced as a replication intermediate in the viral life cycle. First, latent 2′-5′-oligoadenylate synthetase is activated by dsRNA to increase synthesis of 2′-5′ oligoadenylates that are required to activate 2′-5′-A-dependent RNase L (2). Activated RNase L nonspecifically degrades single-stranded RNAs and thus limits virus production. Second, the dsRNA-activated protein kinase (PKR), the most well characterized IFN-induced gene product, mediates the antiviral actions of type I IFNs. In studies reported in this issue of PNAS, Lau and coworkers (3) show that reduction in PKR level acts to delay cell death and thereby converts a lytic infection by encephalomyocarditis virus (EMCV) into a persistent infection. These studies as well as those from other laboratories support the idea that viral pathogenesis may be mediated by PKR-induced cell death and suggest that modification of PKR function in vivo may be a feasible approach to influence viral pathogenesis. In addition, the study presents a model system that may be applied to study mechanisms responsible for the establishment of persistent infections for other viruses such as HIV and hepatitis C virus.
Assessment of Inflammation in an Acute on Chronic Model of Inflammatory Bowel Disease with Ultrasound Molecular Imaging (2015)

Acute inflammation can be accurately measured in a clinically relevant murine model of chronic IBD using ultrasound molecular imaging with a dual P- and E- selectin-targeted contrast agent.
Characterization of the Active Site of ADP-ribosyl Cyclase (1999)

ADP-ribosyl cyclase synthesizes two Ca(2+) messengers by cyclizing NAD to produce cyclic ADP-ribose and exchanging nicotinic acid with the nicotinamide group of NADP to produce nicotinic acid adenine dinucleotide phosphate. Recombinant Aplysia cyclase was expressed in yeast and co-crystallized with a substrate, nicotinamide. x-ray crystallography showed that the nicotinamide was bound in a pocket formed in part by a conserved segment and was near the central cleft of the cyclase. Glu(98), Asn(107) and Trp(140) were within 3.5 A of the bound nicotinamide and appeared to coordinate it. Substituting Glu(98) with either Gln, Gly, Leu, or Asn reduced the cyclase activity by 16-222-fold, depending on the substitution. The mutant N107G exhibited only a 2-fold decrease in activity, while the activity of W140G was essentially eliminated. The base exchange activity of all mutants followed a similar pattern of reduction, suggesting that both reactions occur at the same active site. In addition to NAD, the wild-type cyclase also cyclizes nicotinamide guanine dinucleotide to cyclic GDP-ribose. All mutant enzymes had at least half of the GDP-ribosyl cyclase activity of the wild type, some even 2-3-fold higher, indicating that the three coordinating amino acids are responsible for positioning of the substrate but not absolutely critical for catalysis. To search for the catalytic residues, other amino acids in the binding pocket were mutagenized. E179G was totally devoid of GDP-ribosyl cyclase activity, and both its ADP-ribosyl cyclase and the base exchange activities were reduced by 10,000- and 18,000-fold, respectively. Substituting Glu(179) with either Asn, Leu, Asp, or Gln produced similar inactive enzymes, and so was the conversion of Trp(77) to Gly. However, both E179G and the double mutant E179G/W77G retained NAD-binding ability as shown by photoaffinity labeling with [(32)P]8-azido-NAD. These results indicate that both Glu(179) and Trp(77) are crucial for catalysis and that Glu(179) may indeed be the catalytic residue.
Intracellular and extracellular tau (2010)

In this short review is described the toxicity of modified intracellular tau and that of extracellular tau that could be released into the extracellular space after neuron death.
Linear, annular, and radial focusing with axicons and applications to laser machining (1978)

New optical combinations of axicons and axicons with spherical mirrors and lenses suitable for laser machining are presented. Linear and annular focusing, coaxially and radially to the laser beam, are possible. Most combinations allow continuous adjustment of exit beam parameters, focal line length, focal ring diameter, and magnification, by varying the relative position of one of the axicons. Potential new laser applications are also discussed in relation to these optical devices.
mTOR function and therapeutic targeting in breast cancer. (2017)

The mTOR pathway was discovered in the late 1970s after the compound and natural inhibitor of mTOR, rapamycin was isolated from the bacterium <i>Streptomyces hygroscopicus.</i> mTOR is serine/threonine kinase belonging to the phosphoinositide 3-kinase related kinase (PIKK) family. It forms two distinct complexes; mTORC1 and mTORC2. mTORC1 has a key role in regulating protein synthesis and autophagy whilst mTORC2 is involved in regulating kinases of the AGC family. mTOR signaling is often over active in multiple cancer types including breast cancer. This can involve mutations in mTOR itself but more commonly, in breast cancer, this is related to an increase in activity of ErbB family receptors or alterations and mutations of PI3K signaling. Rapamycin and its analogues (rapalogues) bind to the intercellular receptor FKBP12, and then predominantly inhibit mTORC1 signaling via an allosteric mechanism. Research has shown that inhibition of mTOR is a useful strategy in tackling cancers, with it acting to slow tumor growth and limit the spread of a cancer. Rapalogues have now made their way into the clinic with the rapalogue everolimus (RAD-001/Afinitor) approved for use in conjunction with exemestane, in post-menopausal breast cancer patients with advanced disease who are HER-2 negative (normal expression), hormone receptor positive and whose prior treatment with non-steroidal aromatase inhibitors has failed. Testing across multiple trials has proven that everolimus and other rapalogues are a viable way of treating certain types of cancer. However, rapalogues have shown some drawbacks both in research and clinically, with their use often activating feedback pathways that counter their usefulness. As such, new types of inhibitors are being explored that work via different mechanisms, including inhibitors that are ATP competitive with mTOR and which act to perturb signaling from both mTOR complexes.
Antifungal activity of thyme (Thymus vulgaris L.) essential oil and thymol against moulds from damp dwellings (2006)

Essential oil of thyme and thymol could be used for disinfection of mouldy walls in the dwellings in low concentration.
Paradoxical stimulation of normal and leukemic rat hematopoiesis by monoclonal antibody to CSF-1 receptor. (1996)

We have recently developed a rat monoclonal antibody directed against the murine M-CSF receptor (c-fms). This reagent also inhibits in vitro colony formation by leukemic and normal rat splenocytes in response to M-CSF. At high antibody concentrations, the antibody augments, rather than inhibits, colony formation by rat cells in the presence of M-CSF, an effect that is not seen when murine cells are used as responders. The costimulatory and inhibitory activities of the monoclonal antibody preparations copurify in a number of purification methods, indicating that the costimulatory activity is intrinsic to the antireceptor antibody. Conversion of the antibody into monovalent Fab fragments by papain digestion destroys costimulatory activity. This finding raises a cautionary note for the in vivo use of intact monoclonal antibodies directed against growth factor receptors for the treatment of hematologic malignancies.
Learning word meanings and descriptive parameter spaces from music (2003)

The audio bitstream in music encodes a high amount of statistical, acoustic, emotional and cultural information. But music also has an important linguistic accessory; most musical artists are described in great detail in record reviews, fan sites and news items. We highlight current and ongoing research into extracting relevant features from audio and simultaneously learning language features linked to the music. We show results in a "query-by-description" task in which we learn the perceptual meaning of automatically-discovered single-term descriptive components, as well as a method of automatically uncovering 'semantically attached' terms (terms that have perceptual grounding.) We then show recent work in 'semantic basis functions' --- parameter spaces of description (such as fast ... slow or male ... female) that encode the highest descriptive variance in a semantic space.
Deep Learning Convolutional Neural Network for Speech Recognition: A Review (2021)

In the last few decades, there has been considerable amount of research on the use of Machine Learning (ML) for speech recognition based on Convolutional Neural Network (CNN). These studies are generally focused on using CNN for applications related to speech recognition. Additionally, various works are discussed that are based on deep learning since its emergence in the speech recognition applications. Comparing to other approaches, the approaches based on deep learning are showing rather interesting outcomes in several applications including speech recognition, and therefore, it attracts a lot of researches and studies. In this paper, a review is presented on the developments that occurred in this field while also discussing the current researches that are being based on the topic currently.
The physiological and pharmacological roles of cytochrome P450 isoenzymes (1999)

The cytochrome P450 isoenzymes are a superfamily of haemoprotein enzymes that catalyse the metabolism of a large number of endogenous and exogenous compounds. Recently, the cytochrome isoenzymes have been shown to be important in the synthesis of steroid hormones and bile acids, the arachidonic acid cascade and in central nervous function. These enzymes are a major determinant of the pharmacokinetic behaviour of numerous drugs. Furthermore, alterations in cytochrome P450 activity have been implicated in some diseases.
Three-dimensional micro-computed tomographic evaluation of periodontal regeneration: a human report of intrabony defects treated with Bio-Oss collagen. (2005)

This study utilized three-dimensional micro-computed tomography (micro-CT) to evaluate the regenerative response to Bio-Oss Collagen when used alone or in combination with a Bio-Gide bilayer collagen membrane for the treatment of four intrabony defects (5 to 7 mm) around single-rooted teeth. The micro-CT observations are compared to the clinical, radiographic, and histologic results, which have been previously reported. After reflecting a full-thickness flap, thorough degranulation and root planing were accomplished. Bio-Oss Collagen was then used to fill the defects, and in two cases a Bio-Gide membrane was placed over the filled defect. Radiographs, clinical probing depths, and attachment levels were obtained before treatment and immediately preceding en bloc resection of teeth and surrounding tissues 9 months later. A mean pocket depth reduction of 5.75 mm and mean clinical attachment level gain of 5.25 mm were recorded. The histologic evaluation demonstrated the formation of a complete new attachment apparatus with new cementum, periodontal ligament, and alveolar bone at the level of and coronal to the calculus reference notch. Micro-CT evaluation confirmed the histologic results and demonstrated the absence of ankylosis or root resorption for all specimens. This human histologic study demonstrated that Bio-Oss Collagen has the capacity to facilitate regeneration of the periodontal attachment apparatus when placed in intrabony defects. Micro-CT observations confirmed the histologic results and enhanced the three-dimensional understanding of periodontal wound healing. The results indicate that micro-CT may be useful for three-dimensional evaluation of periodontal regenerative procedures.
Axonal injury in the optic nerve: a model simulating diffuse axonal injury in the brain (1989)

A new model of traumatic axonal injury has been developed by causing a single, rapid, controlled elongation (tensile strain) in the optic nerve of the albino guinea pig. Electron microscopy demonstrates axonal swelling, axolemmal blebs, and accumulation of organelles identical to those seen in human and experimental brain injury. Quantitative morphometric studies confirm that 17% of the optic nerve axons are injured without vascular disruption, and horseradish peroxidase (HRP) studies confirm alterations in rapid axoplasmic transport at the sites of injury. Since 95% to 98% of the optic nerve fibers are crossed, studies of the cell bodies and terminal fields of injured axons can be performed in this model. Glucose utilization was increased in the retina following injury, confirming electron microscopic changes of central chromatolysis in the ganglion cells and increased metabolic activity in reaction to axonal injury. Decreased activity at the superior colliculus was demonstrated by delayed HRP arrival after injury. The model is unique because it produces axonal damage that is morphologically identical to that seen in human brain injury and does so by delivering tissue strains of the same type and magnitude that cause axonal damage in the human. The model offers the possibility of improving the understanding of traumatic damage of central nervous system (CNS) axons because it creates reproducible axonal injury in a well-defined anatomical system that obviates many of the difficulties associated with studying the complex morphology of the brain.
Clinical aspects of altered glycosylation of glycoproteins in cancer (1999)

Alteration of the expression of carbohydrate structures is frequently observed in tumor cells. This review summarizes the different changes of O- and N-linked glycoproteins observed in cancer cells, the impact of the tumor-related carbohydrate phenotypes on the clinical outcome of the cancer disease, and the various ways in which carbohydrate structures can interact with different carbohydrate-detecting adhesion molecules, selectins, and sialoadhesins. Various ways of inhibiting the formation of cell adhesion-engaged carbohydrates on the cell surface, or inhibiting the binding are discussed. Carbohydrate structures which are in clinical use as circulating tumor markers and the effect of genotypes on tumor marker concentrations are reviewed.
Profile-guided proactive garbage collection for locality optimization (2006)

Many applications written in garbage collected languages have large dynamic working sets and poor data locality. We present a new system for continuously improving program data locality at run time with low overhead. Our system proactively reorganizes the heap by leveraging the garbage collector and uses profile information collected through a low-overhead mechanism to guide the reorganization at run time. The key contributions include making a case that garbage collection should be viewed as a proactive technique for improving data locality by triggering garbage collection for locality optimization independently of normal garbage collection for space, combining page and cache locality optimization in the same system, and demonstrating that sampling provides sufficiently detailed data access information to guide both page and cache locality optimization with low runtime overhead. We present experimental results obtained by modifying a commercial, state-of-the-art garbage collector to support our claims. Independently triggering garbage collection for locality optimization significantly improved optimizations benefits. Combining page and cache locality optimizations in the same system provided larger average execution time improvements (17%) than either alone (page 8%, cache 7%). Finally, using sampling limited profiling overhead to less than 3%, on average.