gebhart/patrepeval huggingface dataset:
Murine Mucopolysaccharidosis VII: Impact of Therapies on the Phenotype, Clinical Course, and Pathology in a Model of a Lysosomal Storage Disease (2001)

The mucopolysaccharidoses are a group of lysosomal storage diseases caused by deficiency of an enzyme required for the normal degradation of glycosaminoglycans. Patients with mucopolysaccharidosis typically have widespread lysosomal storage, skeletal and central nervous system disease, and hepatosplenomegaly. Some patients with mucopolysaccharidosis may benefit from enzyme replacement therapy or bone marrow transplantation. Animal models of mucopolysaccharidosis have proven valuable for the evaluation of the effectiveness of potential treatments for patients with lysosomal storage disease. A murine model of MPS VII (Sly syndrome) has proven particularly useful because of its well-defined genetics and its well-characterized clinical, pathologic, and biochemical alterations, which resemble those seen in patients with mucopolysaccharidosis. Correction of these alterations forms the basis for evaluation of the effectiveness of novel treatments. A wide range of therapies have been tested using this model, including enzyme replacement therapy, bone marrow, stem cell, and neural progenitor cell transplantation, and a variety of viral-mediated gene therapies. The inferences drawn from these therapeutic studies using the murine MPS VII model are likely generalizable to other lysosomal storage diseases.
<i>Staphylococcus aureus</i> Resistance to Human Defensins and Evasion of Neutrophil Killing via the Novel Virulence Factor Mprf Is Based on Modification of Membrane Lipids with <scp>l</scp>-Lysine (2001)

Defensins, antimicrobial peptides of the innate immune system, protect human mucosal epithelia and skin against microbial infections and are produced in large amounts by neutrophils. The bacterial pathogen Staphylococcus aureus is insensitive to defensins by virtue of an unknown resistance mechanism. We describe a novel staphylococcal gene, mprF, which determines resistance to several host defense peptides such as defensins and protegrins. An mprF mutant strain was killed considerably faster by human neutrophils and exhibited attenuated virulence in mice, indicating a key role for defensin resistance in the pathogenicity of S. aureus. Analysis of membrane lipids demonstrated that the mprF mutant no longer modifies phosphatidylglycerol with l-lysine. As this unusual modification leads to a reduced negative charge of the membrane surface, MprF-mediated peptide resistance is most likely based on repulsion of the cationic peptides. Accordingly, inactivation of mprF led to increased binding of antimicrobial peptides by the bacteria. MprF has no similarity with genes of known function, but related genes were identified in the genomes of several pathogens including Mycobacterium tuberculosis, Pseudomonas aeruginosa, and Enterococcus faecalis. MprF thus constitutes a novel virulence factor, which may be of general relevance for bacterial pathogens and represents a new target for attacking multidrug resistant bacteria.
A 1.544 Mb/s CMOS Line Driver for 22.8 Ohm Load (1989)

A CMOS line driver for the ISDN Primary Access Transceiver IPAT is presented. Operating in bridge configuration a driver pair delivers. 7.2 Vpp output voltage into a differential load of 22.8Ω at a data rate of 1.544 Mb/s (T1 application), using a single 5V supply voltage . The main feature of the single drivers is a control unit which stabilizes the quiescent current in the output stage at 20mA, while the peak output current is 180mA (T1). The circuit can also be logically configurated to deliver 6 Vpp into a differential load of 60Ω with a quiescent current of 7mA and a data rate of 2.048 Mb/s (CEPT application). Because of its large output transistors, the driver pair occupies an area of 6500 square mils in a 2μm p-well technology.
Jitter analysis of high-speed sampling systems (1990)

The jitter of such practical sampling systems as analog-to-digital converters, sample-and-hold circuits, and samplers is discussed. A model for estimating jitter is proposed. In this model, total jitter is composed of sampling circuit jitter, analog input signal jitter, and sampling clock jitter. Using this model, jitter is broken up into three components. To evaluate the model, a precise method for measuring jitter is devised. This method, based on sampling sine-wave signal-to-noise ratio calculations, enables separation of jitter and amplitude noise. The performance limit of converters as evaluated by the model is discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Inhibition of Interactions and Interconversions of Prion Protein Isoforms by Peptide Fragments from the C-terminal Folded Domain (2001)

The formation of protease-resistant prion protein (PrP-res or PrP(Sc)) involves selective interactions between PrP-res and its normal protease-sensitive counterpart, PrP-sen or PrP(C). Previous studies have shown that synthetic peptide fragments of the PrP sequence corresponding to residues 119-136 of hamster PrP (Ha119-136) can selectively block PrP-res formation in cell-free systems and scrapie-infected tissue culture cells. Here we show that two other peptides corresponding to residues 166-179 (Ha166-179) and 200-223 (Ha200-223) also potently inhibit the PrP-res induced cell-free conversion of PrP-sen to the protease-resistant state. In contrast, Ha121-141, Ha180-199, and Ha218-232 were much less effective as inhibitors. Mechanistic analyses indicated that Ha166-179, Ha200-223, and peptides containing residues 119-136 inhibit primarily by binding to PrP-sen and blocking its binding to PrP-res. Circular dichroism analyses indicated that Ha117-141 and Ha200-223, but not non-inhibitory peptides, readily formed high beta-sheet structures when placed under the conditions of the conversion reaction. We conclude that these inhibitory peptides may mimic contact surfaces between PrP-res and PrP-sen and thereby serve as models of potential therapeutic agents for transmissible spongiform encephalopathies.
Dysregulated RasGRP1 Responds to Cytokine Receptor Input in T Cell Leukemogenesis (2012)

Enhanced signaling by the small guanosine triphosphatase Ras is common in T cell acute lymphoblastic leukemia/lymphoma (T-ALL), but the underlying mechanisms are unclear. We identified the guanine nucleotide exchange factor RasGRP1 (Rasgrp1 in mice) as a Ras activator that contributes to leukemogenesis. We found increased RasGRP1 expression in many pediatric T-ALL patients, which is not observed in rare early T cell precursor T-ALL patients with KRAS and NRAS mutations, such as K-Ras[superscript G12D]. Leukemia screens in wild-type mice, but not in mice expressing the mutant K-Ras[superscript G12D] that encodes a constitutively active Ras, yielded frequent retroviral insertions that led to increased Rasgrp1 expression. Rasgrp1 and oncogenic K-Ras[superscript G12D] promoted T-ALL through distinct mechanisms. In K-Ras[superscript G12D] T-ALLs, enhanced Ras activation had to be uncoupled from cell cycle arrest to promote cell proliferation. In mouse T-ALL cells with increased Rasgrp1 expression, we found that Rasgrp1 contributed to a previously uncharacterized cytokine receptor–activated Ras pathway that stimulated the proliferation of T-ALL cells in vivo, which was accompanied by dynamic patterns of activation of effector kinases downstream of Ras in individual T-ALLs. Reduction of Rasgrp1 abundance reduced cytokine-stimulated Ras signaling and decreased the proliferation of T-ALL in vivo. The position of RasGRP1 downstream of cytokine receptors as well as the different clinical outcomes that we observed as a function of RasGRP1 abundance make RasGRP1 an attractive future stratification marker for T-ALL.
Effect of Cavity Architecture on the Surface-Enhanced Emission from Site-Selective Nanostructured Cavity Arrays (2011)

Presented here are studies of the impact of incident angle on surface-enhanced emission from a dye that is located site selectively on a plasmon-active nanocavity array support. Studies were performed for a surface-active luminescent dye selectively assembled on the top surface or on the walls of the voids of nanocavity array substrates. Results show that emission intensities depend on where the dye is located with respect to the void or surface of the nanocavity array and on the dimensions of the cavity. This was interpreted to arise from the presence of void-localized plasmons and surface-localized and -delocalized plasmon modes.
Linear antigenic regions of the structural proteins of human T-cell lymphotropic virus type I detected by enzyme-linked immunosorbent assays using synthetic peptides as antigens (1992)

We synthesized 46 sequential peptides 21 to 39 amino acids long over the structural protein of human T-cell leukemia virus type I (HTLV-I; the p19 and p24 gag protein and the gp46 and p20E env proteins) and tested their reactivities against antibodies in sera from HTLV-I healthy carriers and patients diagnosed as having human T-cell leukemia-lymphoma (ATLL) and myelopathy (HAM) by using an enzyme-linked immunosorbent assay. Of the 46 synthetic peptides, 18 peptides (2 corresponding to the p19 gag protein, 2 corresponding to the p24 gag protein, 8 corresponding to the gp46 env protein, and 6 corresponding to the p20E env protein) reacted with antibodies in the sera from HTLV-I healthy carriers. In particular, the peptides comprising amino acids 100 to 119 and 119 to 130 of the gag and 175 to 199, 213 to 236, 253 to 282, and 288 to 317 of the env proteins reacted with antibodies in sera from more than 30% of HTLV-I healthy carriers. These peptides also showed high reactivities to the antibodies in the sera from patients with ATLL and HAM. The results indicate that the predominant antigenic regions of the structural protein of HTLV-I were located at the C-terminal end of the p19 gag protein and the C-terminal half of the gp46 env protein, and the corresponding peptides proved to be useful antigens in detecting antibodies in the sera from individuals infected with HTLV-I.
Robust control of robot manipulators based on uncertainty and disturbance estimation (2011)

SUMMARY In this work, uncertainty and disturbance estimation (UDE) based robust trajectory tracking controller for rigid link manipulators was proposed. The UDE was employed to estimate the composite uncertainty that comprises the effects of system nonlinearities, external disturbances, and parametric uncertainties. A feedback linearization based controller was designed for trajectory tracking, and the same was augmented by the UDE‐estimated uncertainties to achieve robustness. The resulting controller however required measurement of joint velocities apart from the joint positions. To address the issue, an observer that employed the UDE‐estimated uncertainties for robustness was proposed, giving rise to the UDE‐based controller–observer structure. Closed‐loop stability of the overall system was established. The notable feature of the proposed design was that it neither required accurate plant model nor any information about the uncertainty. Also, the design needed only joint position measurements for its implementation. To demonstrate the effectiveness, simulation results of the proposed approach as applied to the trajectory tracking control of two‐link robotic manipulator and comparison of its performance with some of the well‐known existing controllers were presented. Lastly, hardware implementation of the proposed design for trajectory control of Quanser's single‐link flexible joint module was carried out, and it was shown that the proposed strategy offered a viable approach for designing implementable robust controllers for robots. Copyright © 2011 John Wiley & Sons, Ltd.
Pre-Steady-State Kinetic Analysis of cAMP-Dependent Protein Kinase Using Rapid Quench Flow Techniques (1996)

The phosphorylation of a peptide substrate by the catalytic subunit of cAMP-dependent protein kinase was monitored over short time periods (2-1000 ms) using a rapid quench flow mixing device and a radioactive assay. The production of phosphokemptide [LRRAS(P)LG] as a function of time is characterized by a rapid "burst" phase (250 s-1) followed by a slower, linear phase (L/[E]t = 21 s-1) at 100 microM Kemptide. The amplitude of this "burst" phase varies linearly with the enzyme concentration and represents approximately 100% of the total enzyme concentration, indicating that the "burst" phase is not due to product inhibition. The observed rate constants for the "burst" and linear phases and the "burst" amplitude vary hyperbolically with the substrate concentration. From these dependencies, a maximum "burst" rate constant of 500 +/- 60 s-1 and a Km and Kd for Kemptide of 4.9 +/- 1.4 and 200 +/- 60 microM were determined. The kcat and Km data extracted from the linear portion of the rapid quench flow transients are indistinguishable from those obtained by standard steady-state kinetic analyses using low catalytic subunit concentrations and a spectrophotometric, coupled enzyme assay. Both rate constants for the "burst" and linear phases decreased in the presence of Mn2+. The data imply that the phosphorylation of Kemptide by the catalytic subunit occurs by a mechanism in which the substrate is loosely bound, is rapidly phosphorylated at the active site, and is released at a steady-state rate that is likely controlled by the dissociation rate constant for ADP. The combined pre-steady-state kinetic data establish a comprehensive, kinetic mechanism that predicts all the steady-state kinetic and viscosometric data. This study represents the first chemical observation and characterization of phosphoryl transfer at the active site of a protein kinase and will be useful for further structure-function studies on this and other protein kinases.
Scratchpad memory management for portable systems with a memory management unit (2006)

In this paper,we present a dynamic scratchpad memory allocation strategy targeting a horizontally partitioned memory subsystem for contemporary embedded processors. The memory subsystem is equipped with a memory management unit (MMU), and physically addressed scratchpad memory (SPM)is mapped into the virtual address space. A small minicache is added to further reduce energy consumption and improve performance.Using the MMU's page fault exception mechanism, we track page accesses and copy frequently executed code sections into the SPM before they are executed. Because the minimal transfer unit between the external memory and the SPM is a single memory page, good code placement is of great importance for the success of our method. Based on profiling information, our postpass optimizer divides the application binary into pageable, cacheable, and uncacheable regions. The latter two are placed at fixed locations in the external memory, and only pageable code is copied on demand to the SPM from the external memory. Pageable code is grouped into sections whose sizes are equal to the physical page size of the MMU. We discuss code grouping techniques and also analyze the effect of the minicache on execution time and energy consumption. We evaluate our SPM allocation strategy with twelve embedded applications, including MPEG-4. Compared to a fully-cached configuration, on average we achieve a 12% improvement in runtime performance and a 33% reduction in energy consumption by the memory system.
DNA polymerase δ isolated from <i>Schizosaccharomyces pombe</i> contains five subunits (1997)

DNA polymerase delta (pol delta) plays an essential role in DNA replication, repair, and recombination. We have purified pol delta from Schizosaccharomyces pombe more than 10(3)-fold and demonstrated that the polymerase activity of purified S. pombe pol delta is completely dependent on proliferating cell nuclear antigen and replication factor C. SDS/PAGE analysis of the purified fraction indicated that the pol delta complex consists of five subunits that migrate with apparent molecular masses of 125, 55, 54, 42, and 22 kDa. Western blot analysis indicated that the 125, 55, and 54 kDa proteins are the large catalytic subunit (Pol3), Cdc1, and Cdc27, respectively. The identity of the other two subunits, p42 and p22, was determined following proteolytic digestion and sequence analysis of the resulting peptides. The peptide sequences derived from the p22 subunit indicated that this subunit is identical to Cdm1, previously identified as a multicopy suppressor of the temperature-sensitive cdc1-P13 mutant, whereas peptide sequences derived from the p42 subunit were identical to a previously uncharacterized ORF located on S. pombe chromosome 1.
Synthesis of Estrogenic Isoflavone Derivatives (1954)

Natural estrogens in plants have assumed considerable importance since the demonstration of their presence in subterranean clover by Bennetts (1) in 1946 and the identification of the isoflavone, genistein (V, 4', 5, 7-OH) as the probable substance responsible for some of the estrogenic activity by Curnow and Bennetts (2) in 1952. Earlier the isoflavones were found in soybean meal as genistein glucoside (3) (5), methyl genistein (V, 6',5, 7,-OH,8- CH3), isogenistein (V,6',5,7-OH), tatoin (V,4',5-OH,8-CH3) ( 4), daidzein (V,4',7-OH) and formononetin (V,4'-OCH3,7-OH) (5). Furthermore the isoflavone biochanin A (V, 4'-OCH3, 5, 7-OH) was isolated from chana seed by Bose and Siddique (6) and formononetin from subterranean clover by Bradbury and White (7).
LTE System Performance (2011)

The system performance requirements set for Long Term Evolution (LTE) Release 8 in demanded substantial improvements over Release 6 of UMTS. This chapter summarizes the main technical features of LTE Release 8 that deliver these substantial system capacity enhancements. Evaluation results are then presented for spectral efficiency and coverage for typical LTE macrocell deployment scenarios, known as ‘Case 1’ and ‘Case 3’ with inter-site distances, together with system performance evaluations in test environments defined by the International Telecommunication Union Radiocommunication Sector (ITU-R). The evaluations presented in the chapter focuses on the Indoor Hotspot (InH), Urban Microcell (UMi), Urban Macrocell (UMa) and Rural Macrocell (RMa) deployment scenarios. The Physical Downlink Control CHannel (PDCCH) coverage in the downlink is estimated on the basis of a 44-bit Downlink Control Information (DCI) message with 8 Control Channel Elements (CCEs), while the PUCCH coverage in the uplink is based on a 4-bit CQI report. Controlled Vocabulary Terms long term evolution; macrocell networks; microcell networks
Breaking the allergic response by disrupting antibody glycosylation (2015)

The Journal of Experimental Medicine Monocytes are a heterogeneous population of phagocytic cells that are generated in the bone marrow and released into the bloodstream.There are two main monocyte subsets in mice: "inflammatory" monocytes that are Ly6C hi CCR2 hi CX 3 CR1 low and "alternative" or "patrolling" monocytes that are Ly6C low CCR2 low CX 3 CR1 hi .The process of monocyte recruitment and differentiation is still a matter of controversy.In this issue, Dal-Secco et al. report in situ monocyte reprogramming in the liver, from proinflammatory CCR2 hi CX 3 CR1 low cells into reparative CCR2 low CX 3 CR1 hi cells and show, for the first time, that this occurs at the site of injury.Dal-Secco et al. harnessed the power of imaging technology and fluorescent reporter mice to track monocytes in a model of sterile inflammation in the liver (induced after a 30 µm 3 burn by a thermal probe).In this model, the recruitment of monocytes is dependent on CCR2 present on CCR2 hi CX 3 CR1 low monocytes.Some of these cells were observed patrolling the liver sinusoids in the steady state.Within 24-48 hours, CCR2 hi CX 3 CR1 low monocytes extravasated and formed a ring structure surrounding the necrotic tissue at the site of the injury.These extravascular monocytes started to differentiate and, by 48-72 hours, had lost CCR2 expression and gained CX 3 CR1 and MHC class II expression (CCR2 low CX 3 CR1 hi CD11b hi MHCII hi CD64 hi F4/80 -).Blocking IL-10 and IL-4 delayed this phenotypic transition and impaired wound healing as shown by failure to clear necrotic hepatocytes and failure to deposit collagen.
Applying secure authentication scheme to protect DNS from rebinding attack using proxy (2015)

Internet is critical to both the economy and society in today's world. Domain Name System (DNS) is a key building block of the internet and the DNS hides all technical infrastructures, software and hardware required for the domain name system to function correctly. It allows users to access websites and exchange emails. It runs a strong mechanism to provide the IP address of the internet host name. An attacker can launch rebinding attack when the DNS server sends a query to any particular server on the network. Different types of techniques have been proposed to prevent this attack that all have some pros and also cones. A new technique is proposed in this paper by using security proxy with a hash function. Rebinding attack can be avoided by using this technique. It provides a secured environment for the DNS to communicate with other DNS. While the source DNS are receiving response from any DNS it will authenticate of all the receiving packets and then sends the data to the client. It gives a secure environment for DNS communication. For this purpose 2 different algorithms are used, namely SHA-2 and AES algorithms. First a random ID will be given to the query and then the query is sent to the DNS server.
Amyloid-specific fluorophores for the rapid, sensitive in situ detection of prion contamination on surgical instruments (2007)

Prion diseases or transmissible spongiform encephalopathies (TSEs) are a group of rare, transmissible and fatal neurodegenerative diseases associated with the protein agent (PrP(Sc)). As such, the sensitive and rapid detection of prion PrP(Sc) amyloid on the surface of suspect surgical instruments is of great importance and may even allow remedial action to be taken prior to any further operative intervention and possible iatrogenic transmission. However, conventional PrP(Sc) detection methodologies tend to rely on the inefficient and unreliable removal of suspect material from a surface using swabs or wipes prior to antibody analysis. Here we show how the combination of an advanced light microscope technique, episcopic differential interference contrast/epifluorescence (EDIC/EF) microscopy, and the application of beta-amyloid fluorescent thiazole markers (thioflavin T, thioflavin S) can be used to detect, in situ, submicron (attomole) levels of prion protein amyloid contamination in brain and spleen sections, smears and homogenate on surgical stainless steel surfaces and surgical instruments. This technique, although not specific to an amyloid type, can be used to verify that surgical instruments are substantially free from prion amyloid protein soiling and hence reduce the risk of iatrogenic transmission.