gebhart/patrepeval huggingface dataset:
Analysis of MAGE-3-specific cytolytic T lymphocytes in human leukocyte antigen-A2 melanoma patients. (1997)

The MAGE-3 gene is a member of a multigene family that is selectively expressed by subsets of different human tumor types, including malignant melanoma, but not by normal tissues except for testis and placenta. A cytolytic T lymphocyte (CTL)-defined MAGE-3 antigen, corresponding to the MAGE-3 peptide 271-279 associated with the human leukocyte antigen (HLA)-A2 molecule, has been recently identified using T lymphocytes from a normal individual stimulated in vitro with peptide-pulsed autologous antigen-presenting cells. Because MAGE-3 is expressed in 76% of metastatic melanomas, the HLA-A2-restricted MAGE-3 antigen should be expressed by approximately 37% of Caucasians bearing a metastatic melanoma tumor, thus representing an attractive candidate for the elicitation of specific CTL immune responses in vivo. In this study, we determined the proportion of HLA-A2+ melanoma patients displaying detectable MAGE-3 peptide 271-279-specific CTL precursors in peripheral blood. Peptide-specific CTL populations were obtained from at least 4 of 11 HLA-A2+ patients. Peptide-specific CTL lines derived from these populations readily lysed HLA-A2-positive target cells that were pulsed with MAGE-3 peptide 271-279 at nanomolar concentrations yet were unable to recognize (as assessed by cytolysis and cytokine production) MAGE-3-expressing autologous or allogeneic HLA-A2-positive melanoma lines. Similarly, the CTL lines failed to recognize MAGE-3-negative HLA-A2-positive tumor lines after transfection with the MAGE-3 gene, although they were able to recognize COS-7 cells transfected with MAGE-3. In contrast, HLA-A1-positive melanoma lines transfected with MAGE-3 were efficiently recognized by CTL lines directed against the MAGE-3 peptide 168-176, a known HLA-A1-restricted CTL epitope. These results suggest that the expression level of the MAGE-3 peptide 271-279, unlike that of MAGE-3 peptide 168-176, in melanomas may be too low to allow efficient recognition by specific CTLs. Thus, it appears that despite the presence of CTL precursors against MAGE-3 peptide 271-279 in some HLA-A2+ melanoma patients, the usefulness of this peptide for specific immunotherapy of melanoma may be limited.
A Comparative Analysis of Community Acquired and Hospital Acquired Methicillin Resistant Staphylococcus Aureus (2013)

The prevalence of the HAMRSA was higher than that of the CAMRSA and they showed a higher drug resistance.
Crystal structure of the catalytic domain of DESC1, a new member of the type II transmembrane serine proteinase family (2007)

DESC1 was identified using gene-expression analysis between squamous cell carcinoma of the head and neck and normal tissue. It belongs to the type II transmembrane multidomain serine proteinases (TTSPs), an expanding family of serine proteinases, whose members are differentially expressed in several tissues. The biological role of these proteins is currently under investigation, although in some cases their participation in specific functions has been reported. This is the case for enteropeptidase, hepsin, matriptase and corin. Some members, including DESC1, are associated with cell differentiation and have been described as tumor markers. TTSPs belong to the type II transmembrane proteins that display, in addition to a C-terminal trypsin-like serine proteinase domain, a differing set of stem domains, a transmembrane segment and a short N-terminal cytoplasmic region. Based on sequence analysis, the TTSP family is subdivided into four subfamilies: hepsin/transmembrane proteinase, serine (TMPRSS); matriptase; corin; and the human airway trypsin (HAT)/HAT-like/DESC subfamily. Members of the hepsin and matriptase subfamilies are known structurally and here we present the crystal structure of DESC1 as a first member of the HAT/HAT-like/DESC subfamily in complex with benzamidine. The proteinase domain of DESC1 exhibits a trypsin-like serine proteinase fold with a thrombin-like S1 pocket, a urokinase-type plasminogen activator-type S2 pocket, to accept small residues, and an open hydrophobic S3/S4 cavity to accept large hydrophobic residues. The deduced substrate specificity for DESC1 differs markedly from that of other structurally known TTSPs. Based on surface analysis, we propose a rigid domain association for the N-terminal SEA domain with the back site of the proteinase domain.
Deletion of the C-Terminal Domain of Apolipoprotein A-I Impairs Cell Surface Binding and Lipid Efflux in Macrophage (1999)

The contribution of the amphipathic alpha-helices of apoA-I toward lipid efflux from human skin fibroblasts and macrophage was examined. Four apoA-I mutants were designed, each by deletion of a pair of predicted adjacent helices. Three mutants lacked two consecutive central alpha-helices [Delta(100-143), Delta(122-165), and Delta(144-186)], whereas the final mutant lacked the C-terminal domain [Delta(187-243)]. When compared to recombinant wild-type apoA-I and mutants with central domain deletions, Delta(187-243) exhibited a marked reduction in its ability to promote either cholesterol or phospholipid efflux from THP-1 macrophages. This mutant also demonstrated a decreased ability to bind lipids and to form lipoprotein complexes. In contrast, the four mutants and apoA-I equally supported cholesterol efflux from fibroblasts, albeit with a reduced capacity when compared to macrophages. Delta(187-243) bound poorly to the macrophage cell surface when compared to apoA-I, and competitive binding studies with the central domain and C-terminal deletions mutants showed that only Delta(187-243) did not compete effectively with [(125)I]apoA-I. Omission of PMA during cholesterol loading enhanced cholesterol efflux to both apoA-I (1.5-fold) and the C-terminal deletion mutant (2.5-fold). Inclusion of the Sandoz ACAT inhibitor (58-035) during loading and, in the absence of PMA, increased and equalized cholesterol efflux to apoA-I and Delta(187-243). Surprisingly, omission of PMA during cholesterol loading had minimal effects on the binding of apoA-I or Delta(187-243) to the THP-1 cell surface. Overall, these results show that cholesterol efflux from cells such as fibroblasts does not require any specific sequence between residues 100 and 243 of apoA-I. In contrast, optimal cholesterol efflux in macrophages requires binding of the C-terminal domain of apoA-I to a cell surface-binding site and the subsequent translocation of intracellular cholesterol to an efflux-competent pool.
Crocacin, a new electron transport inhibitor from Chondromyces cracatus (myxobacteria). Production, isolation, physico-chemical and biological properties. (1994)

Crocacin was isolated from the biomass of the myxobacterium Chondromyces crocatus, strain Cm c3. It inhibited the growth of a few Gram-positive bacteria and a wide spectrum of yeasts and molds. In beef heart submitochondrial particles, crocacin blocked the electron transport within the bc1-segment (complex III) and caused a red shift in the reduced spectrum of cytochrome b with a maximum at 569 nm.
Equilibria and Eu2+ Luminescence of Subsolidus Phases Bounded by Ba[sub 3]MgSi[sub 2]O[sub 8], Sr[sub 3]MgSi[sub 2]O[sub 8], and Ca[sub 3]MgSi[sub 2]O[sub 8] (1968)

The incorporation of divalent europium in the compounds Ca3MgSi2Os, SrsMgSi2Os, and BasMgSi2Os produces phosphors of high luminescence yield, These phosphors respond well to both long and short wavelength ultraviolet excitation, as well as to cathode ray bombardment.The peak of the emission band occurs at progressively shorter wavelength and narrows as the radius of the major alkaline earth ion (Ca, Sr, or Ba) is increased.A 1200~ isotherm on compositions intermediate to Sr3MgSi208 and Ba3MgSi208 shows a complete series of crystalline solutions to exist at this temperature.Using an orthorhombic cell the d-spacings of the ( 222) reflection vary continuously from 1.956A for SrsMgSi2Os:Eu 2+ to 2.012A for Ba~MgSi2Os:Eu 2+.The emission spectra of these samples, however, vary in a discontinuous manner.Complete crystalline solution is likewise observed in a 1200~ isotherm for compositions intermediate to Sr3MgSi2Os and Ca~MgSi2Os.Here the d-spacings of the ( 222) reflection from the orthorhombic cell vary continuously from 1.909A for CasMgSi2Os:Eu 2+ to 1.956A for Sr3MgSi2Os:Eu 2+.Again the peak of the emission spectra varies discontinuously with composition even for the complete crystalline solution series.Emission spectra and x-ray diffraction data collected on samples prepared in the 120O~ subsolidus isotherm intermediate in composition to CasMgSi2Os and Ba3MgSi~Os show an intermediate compound to be formed.This compound BaCa2MgSi2Os has luminescent properties which more closely resemble those of the calcium end-member.Several compositions were prepared in the subsolidus, 1200~ isothermal, ternary section bounded by CasMgSi2Os, Sr3MgSi2Os, and Ba3MgSi2Os.The samples prepared show the major feature of the section to be a large single phase region.In general, broadening of spectral energy distributions is observed as compositions move into the ternary section.All the compositions prepared resulted in phosphors of relatively high efficiency.
OpenSurgery for Topological Assemblies (2020)

Surface quantum error-correcting codes are the leading proposal for fault-tolerance within quantum computers. We present OpenSurgery, a scalable tool for the preparation of circuits protected by the surface code operated through lattice surgery. Lattice surgery is considered a resource efficient method to implement surface code computations. Resource efficiency refers to the number of physical qubits and the time necessary for executing a quantum computation. OpenSurgery is a first step towards methods that aid quantum algorithm design informed by the realities of the hardware architectures. OpenSurgery can: 1) lay out arbitrary quantum circuits, 2) estimate the quantum resources used for their execution, 3) visualise the resulting 3D topological assemblies. Source code is available at http://www.github.com/alexandrupaler/opensurgery.
Poststreptococcal reactive arthritis: clinical course and outcome in 15 patients. (2000)

Patients with Group A beta-hemolytic streptococcal infection and articular disease, who do not fulfill the modified Jones criteria for diagnosis of acute rheumatic fever (ARF), have been classified as having poststreptococcal reactive arthritis (PSRA). We reviewed the clinical characteristics, laboratory findings and outcome of 15 patients with PSRA. None of these patients had clinical evidence of carditis. The pattern of joint involvement was variable and included arthritis in five patients and arthralgia in the remaining ten patients. Nine patients were treated with salicylates for one to 16 weeks; the others recovered spontaneously. Usually, the patients with arthralgia responded promptly to salicylates, while the response was poor in patients with arthritis. One patient with monoarthritis developed carditis nine months after his first arthritis attack. Another patient presenting with monoarthritis later had two additional episodes of poststreptococcal reactive arthralgia. It seems there is a wide spectrum of poststreptococcal rheumatic diseases, and patients with PSRA are also at risk for cardiac disease; therefore, prophylactic antibiotic therapy should be considered in these patients.
Synthesis and Structure-Activity Relationships of Side-Chain-Substituted Analogs of the Allylamine Antimycotic Terbinafine Lacking the Central Amino Function (1995)

Terbinafine is a therapeutically used inhibitor of fungal squalene epoxidase that has prompted extensive derivatization programs for structure-activity relationship studies. In the present study, derivatives of terbinafine were synthesized that lack the central tertiary amino group but have polar substitutents at the tert-butyl residue of the side chain. Evaluation of the antifungal potential revealed that representatives of this novel structural type can also exhibit broad antifungal activity, indicating that the central amino function of allylamine antimycotics is not essential for inhibition of fungal growth. Potency appears to correlate with the polarity of the introduced functional groups, while broad antifungal activity seems to be restricted to compounds with basic substituents. The dimethylamino-substituted "carba-analog" of terbinafine (8k) showed the best antimycotic profile within the whole series.
Synthesis and Activity of New Aryl- and Heteroaryl-Substituted Pyrazole Inhibitors of the Transforming Growth Factor-β Type I Receptor Kinase Domain (2003)

Pyrazole-based inhibitors of the transforming growth factor-beta type I receptor kinase domain (TbetaR-I) are described. Examination of the SAR in both enzyme- and cell-based in vitro assays resulted in the emergence of two subseries featuring differing selectivity versus p38 MAP kinase. A common binding mode at the active site has been established by successful cocrystallization and X-ray analysis of potent inhibitors with the TbetaR-I receptor kinase domain.
802.11n: A Survival Guide (2012)

Author Interview with Matthew Gast What made you write the book? When I first started writing about 802.11, wireless networks were cool and promising. The first time I held a Wi-Fi LAN party, the equipment cost several thousand dollars, and we all needed to spend time installing the right software and drivers. Fast forward a decade, and 802.11n has come along. Wi-Fi has grown up. Every computing device you want to interact with just has Wi-Fi built in and some devices, like the iPad, don't even give you the option not to use it. In the middle of the '00s, I would talk about Wi-Fi and say that everybody was going to have two Wi-Fi devices: A laptop and a phone. I was wrong. It's a laptop, tablet, smartphone, and maybe another device or two. Supporting all these devices requires a fast network, and right now, that means 802.11n. Why is your book especially important now? It's only a slight joke to say that there are only two kinds of users. There are those who have iPads, and there are those who want them. Building a robust network to support tablet computing and its rich interactive experience blending text, audio, and video is a challenge. This book teaches you how to do that. What is the single most important thing readers will be able to do after reading your book? Readers will understand the trade-offs involved in building a large-scale wireless network, and how 802.11n's protocol features help them build the network they want. What do you think is on the horizon for your readers? Wireless LANs touch everything in networking. A key enabler of the mobile computing revolution is that small devices can access data and applications stored elsewhere on the network. Providing a solid network connection is the first step towards enabling any network service, whether it is hosted applications, videoconferencing and screen sharing, or electronic learning.
Enzymatic Characterization of the Streptococcal Endopeptidase, IdeS, Reveals That It Is a Cysteine Protease with Strict Specificity for IgG Cleavage Due to Exosite Binding (2004)

Streptococcus pyogenes, an important pathogen in humans, secretes an IgG specific endopeptidase named IdeS. To elucidate the mechanism that is responsible for this specificity, we have here characterized the activity of IdeS in detail. Both gamma chains of human IgG or its Fc fragment were cleaved in the hinge region after Gly236 by IdeS, but other proteins or synthetic peptides containing sequences such as the P(4)-P(1) segment in the IgG cleavage site, or long peptides resembling the IgG hinge, were not hydrolyzed at all. This is likely due to a second binding site interacting with the Fc part of IgG. The lack of IdeS activity on peptide substrates necessitated the development of an assay with IgG as the substrate for kinetic studies. IdeS showed a sigmoidal velocity curve at physiological IgG concentrations, and a declining enzyme rate at higher IgG concentrations. This atypical velocity curve suggests product inhibition and/or allosteric control, which again indicates the presence of an exosite involved in substrate binding. The pseudoequilibrium constant for IdeS hydrolysis of IgG was 90 microM. The enzyme exhibited activity in the pH range of 5.1-7.6, with an optimum at pH 6.6. IdeS was stable above pH 10 but not at acidic pH. It exhibited an activity maximum around 37 degrees C and a decreased thermal stability at 42 degrees C. Iodoacetate and iodoacetamide inhibited IdeS, as expected for a cysteine protease, and biochemical evidence verified this classification. E-64 and chicken cystatin, specific inhibitors of family C1 and C13 cysteine proteases, were without effect on enzyme activity, as were class specific serine, aspartic, and metallo protease inhibitors. No significant similarities were found in protein sequence comparisons with known enzyme families, suggesting that IdeS represents a novel family of cysteine proteases.
Multiple sensors on pulsed eddy-current detection for 3-D subsurface crack assessment (2005)

This paper proposes the use of multiple sensors in pulsed eddy-current detection for three-dimensional (3-D) subsurface flaw imaging. A normalization technique has been proposed to eliminate the characteristic variation among the Hall devices used in the probe and lift off effects. A principal component analysis-based feature extraction that provides orthogonal information for multiple sensor fusion has been introduced and investigated. Using the features of multiple projection coefficients, 3-D surface flaws can be measured and reconstructed. The experimental tests have illustrated that the proposed method has delivered more defect information than the conventional peak value and time for pulsed eddy-current sensors.
Health-related quality of life and posttraumatic stress disorder in survivors of the acute respiratory distress syndrome (1998)

Long-term survivors of ARDS describe a good overall health-related quality of life. Major impairments in mental health domains of health-related quality of life are associated with the development of posttraumatic stress disorder and are a possible result of traumatic experiences during ICU therapy.
DracoSTM (2007)

Transactional memory (TM) is a recent parallel programming concept which reduces challenges found in parallel programming. TM offers numerous advantages over other synchronization mechanisms, yet many current TM systems require complex hardware, programming language extensions, specific compiler support or enforce impractical software design, making these models unrealistic as an immediate TM solution for early adopters. Our new software transactional memory (STM) system, DracoSTM, is a high performance lock-based C++ STM research library. DracoSTM uses only native object-oriented language semantics, increasing its intuitiveness for developers while maintaining high programmability via automatic handling of composition, locks and transaction termination. DracoSTM is the STM first solution to (1) implement both direct and deferred updating and (2) enable run-time alternation between these updating policies. DracoSTM requires no language extension, specific development environment or platform, widening its usability and increasing the novelty of its design. This paper describes DracoSTM from an architectural infrastructure viewpoint. TM-specific and library-specific aspects are discussed, as are their cross-cutting design concerns. Finally, performance benchmarks are presented, showing DracoSTM outperform another high performing C++ STM library, by upwards of two orders of magnitude.
Disruption of the splicing enhancer sequence within exon 27 of the dystrophin gene by a nonsense mutation induces partial skipping of the exon and is responsible for Becker muscular dystrophy. (1997)

The mechanism of exon skipping induced by nonsense mutations has not been well elucidated. We now report results of in vitro splicing studies which disclosed that a particular example of exon skipping is due to disruption of a splicing enhancer sequence located within the exon. A nonsense mutation (E1211X) due to a G to T transversion at the 28th nucleotide of exon 27 (G3839T) was identified in the dystrophin gene of a Japanese Becker muscular dystrophy case. Partial skipping of the exon resulted in the production of truncated dystrophin mRNA, although the consensus sequences for splicing at both ends of exon 27 were unaltered. To determine how E1211X induced exon 27 skipping, the splicing enhancer activity of purine-rich region within exon 27 was examined in an in vitro splicing system using chimeric doublesex gene pre-mRNA. The mutant sequence containing G3839T abolished splicing enhancer activity of the wild-type purine-rich sequence for the upstream intron in this chimeric pre-mRNA. An artificial polypurine oligonucleotide mimicking the purine-rich sequence of exon 27 also showed enhancer activity that was suppressed by the introduction of a T nucleotide. Furthermore, the splicing enhancer activity was more markedly inhibited when a nonsense codon was created by the inserted T residue. This is the first evidence that partial skipping of an exon harboring a nonsense mutation is due to disruption of a splicing enhancer sequence.
Phase 1 Clinical and Pharmacokinetics Evaluation of Oral CI-1033 in Patients with Refractory Cancer (2005)

CI-1033 is suitable for phase 2 testing at the 450 mg/day dose level when administered for 14 days in a 21-day cycle. The pharmacokinetic profile is consistent with biologically relevant plasma concentrations over the dosing interval.
Mechanistic insights into remodeled Tau-derived PHF6 peptide fibrils by Naphthoquinone-Tryptophan hybrids (2018)

Intra-cellular tau protein tangles and extra-cellular β-amyloid plaques are hallmarks of Alzheimer's disease (AD), characterized by the conversion of natively unfolded monomeric protein/peptide into misfolded β-sheet rich aggregates. Therefore, inhibiting the aggregation cascade or disassembling the pre-formed aggregates becomes a pivotal event in disease treatment. In the present study, we show that Naphthoquinone-Tryptophan hybrids, i.e., NQTrp and Cl-NQTrp significantly disrupted the pre-formed fibrillar aggregates of Tau-derived PHF6 (VQIVYK) peptide and full-length tau protein in vitro, in a dose-dependent manner as evident from ThS assay, CD spectroscopy, and TEM. Molecular dynamics simulation of PHF6 oligomers and fibrils with the Naphthoquinone-Tryptophan hybrids provides a possible structure-function based mechanism-of-action, highlighting the role of hydrophobic interaction and hydrogen bond formation during fibril disassembly. These findings signify the effectiveness of NQTrp and Cl-NQTrp in disassembling fibrillar aggregates and may help in designing novel hybrid molecules for AD treatment.
A test of the "jigsaw puzzle" model for protein folding by multiple methionine substitutions within the core of T4 lysozyme. (1996)

To test whether the structure of a protein is determined in a manner akin to the assembly of a jigsaw puzzle, up to 10 adjacent residues within the core of T4 lysozyme were replaced by methionine. Such variants are active and fold cooperatively with progressively reduced stability. The structure of a seven-methionine variant has been shown, crystallographically, to be similar to wild type and to maintain a well ordered core. The interaction between the core residues is, therefore, not strictly comparable with the precise spatial complementarity of the pieces of a jigsaw puzzle. Rather, a certain amount of give and take in forming the core structure is permitted. A simplified hydrophobic core sequence, imposed without genetic selection or computer-based design, is sufficient to retain native properties in a globular protein.