gebhart/patrepeval huggingface dataset:
γ-Secretase Substrate Concentration Modulates the Aβ42/Aβ40 Ratio (2007)

Mutation of the amyloid precursor protein (APP), presenilin-1, or presenilin-2 results in the development of early onset autosomal dominant forms of Alzheimer disease (AD). These mutations lead to an increased Abeta42/Abeta40 ratio that correlates with the onset of disease. However, it remains unknown how these mutations affect gamma-secretase, a protease that generates the termini of Abeta40 and Abeta42. Here we have determined the reaction mechanism of gamma-secretase with wild type and three mutated APP substrates. Our findings indicate that despite the overall outcome of an increased Abeta42/Abeta40 ratio, these mutations each display rather distinct reactivity to gamma-secretase. Intriguingly, we found that the ratio of Abeta42/Abeta40 is variable with substrate concentration; increased substrate concentrations result in higher ratios of Abeta42/Abeta40. Moreover, we demonstrated that reduction of gamma-secretase substrate concentration by BACE1 inhibition in cells decreased the Abeta42/Abeta40 ratio. This study indicates that biological factors affecting targets such as BACE1 and APP, which ultimately cause an increased concentration of gamma-secretase substrate, can augment the Abeta42/Abeta40 ratio and may play a causative role in sporadic AD. Therefore, strategies lowering the Abeta42/Abeta40 ratio through partial reduction of gamma-secretase substrate production may introduce a practical therapeutic modality for treatment of AD.
Ex vivo gene therapy with lentiviral vectors rescues adenosine deaminase (ADA)–deficient mice and corrects their immune and metabolic defects (2006)

Adenosine deaminase (ADA) deficiency is caused by a purine metabolic dysfunction, leading to severe combined immunodeficiency (SCID) and multiple organ damage. To investigate the efficacy of ex vivo gene therapy with self-inactivating lentiviral vectors (LVs) in correcting this complex phenotype, we used an ADA(-/-) mouse model characterized by early postnatal lethality. LV-mediated ADA gene transfer into bone marrow cells combined with low-dose irradiation rescued mice from lethality and restored their growth, as did transplantation of wild-type bone marrow. Mixed chimerism with multilineage engraftment of transduced cells was detected in the long term in animals that underwent transplantation. ADA activity was normalized in lymphocytes and partially corrected in red blood cells (RBCs), resulting in full metabolic detoxification and prevention of severe pulmonary insufficiency. Moreover, gene therapy restored normal lymphoid differentiation and immune functions, including antigen-specific antibody production. Similar degrees of detoxification and immune reconstitution were obtained in mice treated early after birth or after 1 month of enzyme-replacement therapy, mimicking 2 potential applications for ADA-SCID. Overall, this study demonstrates the efficacy of LV gene transfer in correcting both the immunological and metabolic phenotypes of ADA-SCID and supports the future clinical use of this approach.
Thermal and Dynamic Mechanical Properties of Sulfonated Polypentenamers (1980)

A series of sulfonated polypentenamers containing from 1.9 to 17.6 mol % pendant groups in the form of sodium salts was studied by differential scanning calorimetry (DSC) and dynamic mechanical techniques. The composition dependencies of the glass transition temperatures (Tg's) measured by DSC show typical random copolymer behavior at low levels of sulfonation but deviate significantly from this behavior above 10 mol %. The dynamic mechanical results exhibit an ionic-phase relaxation α that is believed to originate within ionic clusters. The fact that the α relaxation is only present in samples sulfonated above 10 mol % is taken as evidence, along with the Tg behavior, that clustering occurs only above a critical sulfonate concentration of 10 mol % or two sulfonate groups per 100 backbone carbon atoms.
Substrate Binding and Intersubunit Interactions in l-Asparaginase (1974)

Abstract d-Asparagine prevents the dissociation of Escherichia colil-asparaginase. Conditions that affect the rate of hydrolysis of the substrate also influence the extent of protection. The most effective stabilization of the tetrameric aggregate is provided between pH 5 and 8 with half-maximal rates of dissociation occurring at pH 4.2 and 8.8. Partial acetylation of tyrosyl residues of l-asparaginase results in modification of behavior of the enzyme towards the protective action of d-asparagine. The results of these studies have provided an indication of the nature of the amino acid residues at the substrate-binding site.
Morphology Transition during Low-Pressure Chemical Vapor Deposition (2001)

Assuming a reemission model, we have studied, in detail, the effect of sticking coefficient on the morphology evolution in low-pressure chemical vapor deposition processes. We have shown that the surface morphology changes from a self-affine fractal to a columnarlike morphology with increasing sticking coefficient, which agrees qualitatively with experimental observations.
Taxonomic Note: A Place for DNA-DNA Reassociation and 16S rRNA Sequence Analysis in the Present Species Definition in Bacteriology (1994)

Because a natural entity “species” cannot be recognized as a group of strains that is genetically well separated from its phylogenetic neighbors, a pragmatic approach was taken to define a species by a polyphasic approach (L. G. Wayne, D. J. Brenner, R. R. Colwell, P. A. D. Grimont, O. Kandler, M. I. Krichevsky, L. H. Moore, W. E. C. Moore, R. G. E. Murray, E. Stackebrandt, M. P. Starr, and H. G. Trüper, Int. J. Syst. Bacteriol. 37:463-464, 1987), in which a DNA reassociation value of about 70% plays a dominant role. With the establishment of rapid sequence analysis of 16S rRNA and the recognition of its potential to determine the phylogenetic position of any prokaryotic organism, the role of 16S rRNA similarities in the present species definition in bacteriology needs to be clarified. Comparative studies clearly reveal the limitations of the sequence analysis of this conserved gene and gene product in the determination of relationships at the strain level for which DNA-DNA reassociation experiments still constitute the superior method. Since today the primary structure of 16S rRNA is easier to determine than hybridization between DNA strands, the strength of the sequence analysis is to recognize the level at which DNA pairing studies need to be performed, which certainly applies to similarities of 97% and higher.
The Opportunistic Pathogen Propionibacterium acnes: Insights into Typing, Human Disease, Clonal Diversification and CAMP Factor Evolution (2013)

We previously described a Multilocus Sequence Typing (MLST) scheme based on eight genes that facilitates population genetic and evolutionary analysis of P. acnes. While MLST is a portable method for unambiguous typing of bacteria, it is expensive and labour intensive. Against this background, we now describe a refined version of this scheme based on two housekeeping (aroE; guaA) and two putative virulence (tly; camp2) genes (MLST4) that correctly predicted the phylogroup (IA1, IA2, IB, IC, II, III), clonal complex (CC) and sequence type (ST) (novel or described) status for 91% isolates (n = 372) via cross-referencing of the four gene allelic profiles to the full eight gene versions available in the MLST database (http://pubmlst.org/pacnes/). Even in the small number of cases where specific STs were not completely resolved, the MLST4 method still correctly determined phylogroup and CC membership. Examination of nucleotide changes within all the MLST loci provides evidence that point mutations generate new alleles approximately 1.5 times as frequently as recombination; although the latter still plays an important role in the bacterium's evolution. The secreted/cell-associated 'virulence' factors tly and camp2 show no clear evidence of episodic or pervasive positive selection and have diversified at a rate similar to housekeeping loci. The co-evolution of these genes with the core genome might also indicate a role in commensal/normal existence constraining their diversity and preventing their loss from the P. acnes population. The possibility that members of the expanded CAMP factor protein family, including camp2, may have been lost from other propionibacteria, but not P. acnes, would further argue for a possible role in niche/host adaption leading to their retention within the genome. These evolutionary insights may prove important for discussions surrounding camp2 as an immunotherapy target for acne, and the effect such treatments may have on commensal lineages.
A shell for modern personal computers (1987)

Over the last five years, the average personal computer has changed radically in both power and typical peripherals. The command interpreters on these machines have not changed to reflect this. The following paper describes a command interpreter designed for a modern personal computer, with a high speed 16/32 bit processor, a megabyte or more of memory, a medium resolution bitmapped display, and a pointing device.
Glycoproteins of 210,000 and 130,000 m.w. on activated T cells: cell distribution and antigenic relation to components on resting cells and T cell lines. (1984)

A glycoprotein complex of 210,000 and 130,000 m.w., found on mitogen or alloantigen-stimulated human T cells and not on other hematopoietic cells, has been defined by a monoclonal antibody (Mab). The components of this complex are a subset of a larger family of proteins (210,000, 165,000 and 130,000 m.w.) defined by a second Mab. In a panel of hematopoietic cell lines and cell types, only activated T cells (including the cell line HUT-102) express the 210,000/130,000 complex and these cells also express the IL 2 receptor, a characteristic marker for activated T cells. The 210,000/130,000 m.w. complex (reactive with the Mab TS2/7) is present on all long-term activated T cells, including both the OKT4 and OKT8 subsets. The 210,000 m.w. subunit is expressed only on activated T cells. Other lymphoid cells express either the 130,000 m.w. subunit alone (unactivated lymphocytes, thymocytes, HUT-78) or the 130,000 subunit together with a 165,000 subunit (MOLT-4, HSB, and other leukemic T cell lines). The 210,000/130,000 m.w., 165,000/130,000 m.w. and 130,000 m.w. complexes are antigenically related in that all share reactivity with the Mab A- 1A5 . Among non-lymphoid hematopoietic cells and cell lines, none express the 210,000 m.w. chain; adherent cells (monocytes) and myeloid cell lines each express single proteins of 130,000 to 155,000 m.w. Granulocytes and red blood cells are negative and platelets express multiple bands (165,000 and 140,000 m.w.). Immunoperoxidase staining of tissue sections showed that a broad range of tissues and cell types had material cross-reactive with the lymphoid 130,000 m.w. protein. However, only a discrete subset of those tissues and cells including blood vessel walls, connective tissue, smooth muscle, kidney mesangial cells, and some non-cellular matrix tissue, had material cross-reactive with the 210,000 m.w. protein on activated T lymphocytes.
Prediction-Based Throughput Optimization for Dynamic Spectrum Access (2010)

Cognitive radio (CR) for dynamic spectrum sensing and access has been a hot research topic in recent years. To avoid collision with the primary users, secondary users need to sense the channels before transmitting on them, which is referred to as sensing time overhead. Our previous work shows that the spectral correlations between the channels within the same service are sufficiently high for accurate prediction, which can further be used to reduce the sensing time. With such motivation, in this paper, we propose a new definition, i.e., channel availability vector (CAV), to characterize the state information of a group of licensed channels by introducing spectrum prediction while focusing on the scenario of a single secondary user with multiple channels and leverage it by formulating the throughput optimization problem as a Markov decision process, which is further solved by our optimal sensing scheme and verified with the real spectrum measurement data. The results show that our prediction-based sensing scheme outperforms one existing work.
Retinal Nerve Fiber Layer Segmentation on FD-OCT Scans of Normal Subjects and Glaucoma Patients (2010)

Automated measurements of the retinal nerve fiber layer thickness on circular OCT B-Scans provide physicians additional parameters for glaucoma diagnosis. We propose a novel retinal nerve fiber layer segmentation algorithm for frequency domain data that can be applied on scans from both normal healthy subjects, as well as glaucoma patients, using the same set of parameters. In addition, the algorithm remains almost unaffected by image quality. The main part of the segmentation process is based on the minimization of an energy function consisting of gradient and local smoothing terms. A quantitative evaluation comparing the automated segmentation results to manually corrected segmentations from three reviewers is performed. A total of 72 scans from glaucoma patients and 132 scans from normal subjects, all from different persons, composed the database for the evaluation of the segmentation algorithm. A mean absolute error per A-Scan of 2.9 µm was achieved on glaucomatous eyes, and 3.6 µm on healthy eyes. The mean absolute segmentation error over all A-Scans lies below 10 µm on 95.1% of the images. Thus our approach provides a reliable tool for extracting diagnostic relevant parameters from OCT B-Scans for glaucoma diagnosis.
Reducing amplification artifacts in high multiplex amplicon sequencing by using molecular barcodes (2015)

We demonstrated the successful implementation of molecular barcodes in high multiplex PCR, with multiplex scale many times higher than earlier work. We showed that the new protocol combines the benefits of both high multiplex PCR and molecular barcodes, i.e. the analysis of a very large region, low DNA input requirement, very good reproducibility and the ability to detect as low as 1% mutations with minimal false positives (FP).
Synthesis of Aromatic Ketones by a Transition Metal-Catalyzed Tandem Sequence (2006)

Both simple Ag(I) and Au(I) are effective catalysts for a tandem [3,3]-sigmatropic rearrangement/formal Myers-Saito cyclization of propargyl esters to form aromatic ketones. A mechanism in which the metal catalyzes both of these processes through alkyne activation is proposed. By using this method a wide range of aromatic structures including naphthyl, anthracenyl and indole ketones are available from readily available propargyl esters.
Glucose starvation alters lipid-linked oligosaccharide biosynthesis in Chinese hamster ovary cells. (1981)

The effect of glucose deprivation on the synthesis of lipid-linked oligosaccharides by Chinese hamster ovary cells has been studied. When these cells are placed in serum-free Dulbecco's minimal essential medium devoid of glucose, there is a rapid cessation of the synthesis of the usual Glc3Man9GlcNAc2 lipid-linked oligosaccharide and the accumulation of a smaller species with the composition Man9GlcNAc2. This latter compound is the glucosylated and transferred to protein where it is subsequently processed. These findings demonstrate that Chinese hamster ovary cells utilize an alternate glycosylation pathway when deprived of glucose.
Clinical outcomes of combined versus separate carbachol and brimonidine drops in correcting presbyopia (2016)

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Learning and Memory and Synaptic Plasticity Are Impaired in a Mouse Model of Rett Syndrome (2006)

Loss-of-function mutations or abnormal expression of the X-linked gene encoding methyl CpG binding protein 2 (MeCP2) cause a spectrum of postnatal neurodevelopmental disorders including Rett syndrome (RTT), nonsyndromic mental retardation, learning disability, and autism. Mice expressing a truncated allele of Mecp2 (Mecp2(308)) reproduce the motor and social behavior abnormalities of RTT; however, it is not known whether learning deficits are present in these animals. We investigated learning and memory, neuronal morphology, and synaptic function in Mecp2(308) mice. Hippocampus-dependent spatial memory, contextual fear memory, and social memory were significantly impaired in Mecp2(308) mutant males (Mecp2(308/Y)). The morphology of dendritic arborizations, the biochemical composition of synaptosomes and postsynaptic densities, and brain-derived neurotrophic factor expression were not altered in these mice. However, reduced postsynaptic density cross-sectional length was identified in asymmetric synapses of area CA1 of the hippocampus. In the hippocampus of symptomatic Mecp2(308/Y) mice, Schaffer-collateral synapses exhibited enhanced basal synaptic transmission and decreased paired-pulse facilitation, suggesting that neurotransmitter release was enhanced. Schaffer-collateral long-term potentiation (LTP) was impaired. LTP was also reduced in the motor and sensory regions of the neocortex. Finally, very early symptomatic Mecp2(308/Y) mice had increased basal synaptic transmission and deficits in the induction of long-term depression. These data demonstrate a requirement for MeCP2 in learning and memory and suggest that functional and ultrastructural synaptic dysfunction is an early event in the pathogenesis of RTT.
Cancer Statistics, 2001 (2001)

Each year the American Cancer Society compiles estimates of the number of new cancer cases and deaths expected in the US in the current year and the most recent data on cancer incidence, mortality, and survival. An estimated 1,268,000 new cases of cancer will be diagnosed in the year 2001 and an estimated 553,400 Americans will die from cancer. Overall cancer incidence and death rates have continued to decrease in men and women since the early 1990s, and the decline in overall cancer mortality has been greater in recent years. Despite reductions in age-adjusted rates of cancer death, the total number of recorded cancer deaths in the US continues to increase, due to an aging and expanding population. Large disparities in cancer incidence and mortality across racial/ethnic groups continue. Black men and women experience higher incidence of cancer and poorer survival than white men and women. The disparity in survival reflects both diagnosis of cancer at later disease stages, and poorer survival within each stage of diagnosis.
RF INDUCTION EXCITATION OF CW VISIBLE LASER TRANSITIONS IN IONIZED GASES (1966)

Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter Facebook Reddit LinkedIn Tools Icon Tools Reprints and Permissions Cite Icon Cite Search Site Citation J. P. Goldsborough, E. B. Hodges, W. E. Bell; RF INDUCTION EXCITATION OF CW VISIBLE LASER TRANSITIONS IN IONIZED GASES. Appl. Phys. Lett. 15 March 1966; 8 (6): 137–139. https://doi.org/10.1063/1.1754523 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAIP Publishing PortfolioApplied Physics Letters Search Advanced Search |Citation Search
Three-dimensional displays (1980)

Three-dimensional display techniques can be classified as binocular and autostereoscopic types, still and animated types, nontransmitted and transmitted types, and nonholographic and holographic types. This paper deals mainly with autostereoscopic still nontransmitted techniques. Holographic and nonholographic tecniques are described on about equal footing. For the sake of brevity, emphasis is placed upon those techniques that appeared in the past several years. However, some old techniques of historical and/or practical importance are also mentioned because rather few textbooks are available in this field. In the final part, state of the art of three-dimensional display for animated and transmitted images (three-dimensional television) is described. Speculations on the direction of the development are presented.
Use of Decision Support Techniques for Information System Risk Management (2008)

Abstract Identifying and understanding security risks for information system design or evaluation is very challenging. Making decisions about accepting or mitigating these risks through a rational, traceable, and understandable process is even harder. Quantitative risk analysis techniques can help stakeholders understand and communicate risk‐informed design decisions even when the stakeholders have conflicting objectives. Quantitative risk analysis also helps stakeholders understand security, cost, and functionality trade‐off decisions in repeatable process. This paper discusses the roles of stakeholders in risk analysis, the advantages and disadvantages of quantitative risk analysis, basic cyber risk decision support concepts and processes, and the mathematical definitions of risk for information systems. This paper recommends the use of properly constructed quantitative risk analysis models and discourages the use of semiquantitative risk analysis models.
Functional interaction of Oct transcription factors with the family of repeats in Epstein–Barr virus oriP (2005)

The family of repeats (FR) is a major upstream enhancer of the Epstein-Barr virus (EBV) latent C promoter (Cp) that controls transcription of six different latent nuclear proteins following interaction with the EBV nuclear protein EBNA1. Here, it was shown that Cp could also be activated by octamer-binding factor (Oct) proteins. Physical binding to the FR by the cellular transcription factors Oct-1 and Oct-2 was demonstrated by using an electrophoretic mobility-shift assay. Furthermore, Oct-1 in combination with co-regulator Bob.1, or Oct-2 alone, could drive transcription of a heterologous thymidine kinase promoter linked to the FR in both B cells and epithelial cells. Cp controlled by the FR was also activated by binding of Oct-2 to the FR. This may have direct implications for B cell-specific regulation of Cp.
Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients (2004)

Taxol produces neuropathic pain with three distinct zones of involvement in the extremities. Most distally is an area of on-going pain and proximal to this is a zone of sensory disturbance but not overt pain. These two areas were confined in all but one case to the glabrous skin of the hands and/or feet. More proximal is an area not recognized by the patients as involved with pain or sensory disturbance yet wherein quantitative sensory tests nevertheless reveal altered sensibility. Impairment of perception to light touch, normally conveyed by myelinated fibers, was dramatically altered in all three areas, being approximately 50-fold greater than normal in areas of pain and sensory disturbance as well as in areas of skin perceived by the patients as not affected. Impairment of perception to sharpness, normally conveyed by small myelinated fibers, was most pronounced in areas of on-going pain, intermediate in areas of sensory disturbance and near baseline in more proximal skin of chemotherapy patients. In contrast to mechanical sensibility, thermal thresholds for warm and heat pain detection were normal throughout. Finally, chemotherapy patients showed paradoxical burning pain to skin cooling that was most pronounced in proximal areas of skin thought to be unaffected by the patients, intermediate in the border zone of altered sensibility and least pronounced in areas of on-going pain. These data suggest that taxol produces a neuropathy characterized by pronounced impairment of function in A-beta myelinated fibers, intermediate impairment of A-delta myelinated fibers, and a relative sparing of C-fibers.