gebhart/patrepeval huggingface dataset:
A macromolecular delivery vehicle for protein-based vaccines: Acid-degradable protein-loaded microgels (2003)

The development of protein-based vaccines remains a major challenge in the fields of immunology and drug delivery. Although numerous protein antigens have been identified that can generate immunity to infectious pathogens, the development of vaccines based on protein antigens has had limited success because of delivery issues. In this article, an acid-sensitive microgel material is synthesized for the development of protein-based vaccines. The chemical design of these microgels is such that they degrade under the mildly acidic conditions found in the phagosomes of antigen-presenting cells (APCs). The rapid cleavage of the microgels leads to phagosomal disruption through a colloid osmotic mechanism, releasing protein antigens into the APC cytoplasm for class I antigen presentation. Ovalbumin was encapsulated in microgel particles, 200-500 nm in diameter, prepared by inverse emulsion polymerization with a synthesized acid-degradable crosslinker. Ovalbumin is released from the acid-degradable microgels in a pH-dependent manner; for example, microgels containing ovalbumin release 80% of their encapsulated proteins after 5 h at pH 5.0, but release only 10% at pH 7.4. APCs that phagocytosed the acid-degradable microgels containing ovalbumin were capable of activating ovalbumin-specific cytoxic T lymphocytes. The acid-degradable microgels developed in this article should therefore find applications as delivery vehicles for vaccines targeted against viruses and tumors, where the activation of cytoxic T lymphocytes is required for the development of immunity.
Isoprenoid biosynthesis in plants – 2C‐methyl‐d‐erythritol‐4‐phosphate synthase (IspC protein) of Arabidopsis thaliana (2006)

The ispC gene of Arabidopsis thaliana was expressed in pseudomature form without the putative plastid-targeting sequence in a recombinant Escherichia coli strain. The recombinant protein was purified by affinity chromatography and was shown to catalyze the formation of 2C-methyl-D-erythritol 4-phosphate from 1-deoxy-D-xylulose 5-phosphate at a rate of 5.6 micromol x min(-1) x mg(-1) (k(cat) 4.4 s(-1)). The Michaelis constants for 1-deoxy-D-xylulose 5-phosphate and the cosubstrate NADPH are 132 and 30 microm, respectively. The enzyme has an absolute requirement for divalent metal ions, preferably Mn2+ and Mg2+, and is inhibited by fosmidomycin with a Ki of 85 nm. The pH optimum is 8.0. NADH can substitute for NADPH, albeit at a low rate (14% as compared to NADPH). The enzyme catalyzes the reverse reaction at a rate of 2.1 micromol x min(-1) x mg(-1).
Role of PGE2 and EP Receptors in the Pathogenesis of Rheumatoid Arthritis and as a Novel Therapeutic Strategy (2006)

Recent progress in understanding the pathogenesis of rheumatoid arthritis (RA) in parallel with elucidation of the functional role of the prostaglandin receptor subfamily has revealed an important regulatory role of PGE2, in addition to its well-known proinflammatory role in the progression of RA. Characteristic features of RA are synovial proliferation and pannus formation, which result in the destruction of cartilage and bone. Pannus tissue is mainly composed of macrophages and fibroblast-like synoviocytes. Both T cell-derived IL-17 and macrophage-derived TNF-alpha seem to play a central role in the progression of proinflammatory cascades in RA. PGE2 is also produced in response to proinflammatory cytokines, which in turn negatively regulates both IL-17 and TNF-alpha expression and TNF/IL-1-induced activation of fibroblast-like synoviocytes through EP2/EP4 receptors, resulting in the modulation of proinflammatory cascades. IL-17- and TNF-activated macrophages differentiate into osteoclasts in the presence of M-CSF and RANKL expressed by fibroblast-like synoviocytes. PGE2 binding to EP4 stimulates osteoclastogenesis through enhancing RANKL expression. At the same time, PGE2 suppresses osteoclastogenesis by inhibiting M-CSF expression of fibroblast-like synoviocytes as well as both IL-17 and IL-17-induced TNF-alpha expression of macrophages. PGE2-EP4 also activates osteoblastogenesis through increasing cbfa1 and osterix, two essential transcription factors required for bone formation. The net effect of PGE2 may direct toward repair of eroding bone through the suppression of inflammation and enhancement of bone remodeling. Here, we discuss a diverse action of PGE2/EP receptors and their important regulatory roles in the pathogenesis of RA, which may lead to a novel therapeutic strategy.
Varicose veins associated with CADASIL result from a novel mutation in the Notch3 gene (2006)

No genetically diagnosed cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) pedigrees with venous insufficiency have been described. In a CADASIL pedigree with varicose veins, the authors have identified a novel heterozygous mutation in the 3' splice acceptor site of intron 15 of the Notch3 gene. This, based on mRNA analysis, resulted in skipping of exon 16 including eight cysteine residues of EGF-like repeats.
168 Gb/s/λ Direct-Detection 64-QAM SSB Nyquist-SCM Transmission over 80 km Uncompensated SSMF at 4.54 b/s/Hz net ISD using a Kramers-Kronig Receiver (2017)

Using the recently-proposed Kramers-Kronig receiver DSP scheme, we achieved 4×168 Gb/s 35 GHz-spaced WDM single-polarization direct-detection 64-QAM SSB Nyquist-SCM transmission over 80 km of uncompensated SSMF at a record net ISD of 4.54 b/s/Hz.
XQuery reloaded (2009)

This paper describes a number of XQuery-related projects. Its goal is to show that XQuery is a useful tool for many different application scenarios. In particular, this paper tries to correct a common myth that XQuery is merely a query language and that SQL is the better query language. Instead, XQuery is a full-fledged programming language for Web applications and services. Furthermore, this paper tries to correct a second myth that XQuery is slow. This paper gives an overview of the state-of-the-art in XQuery implementation and optimization techniques and discusses one particular open-source XQuery processor, Zorba, in more detail. Among others, this paper presents an XQuery Benchmark Service which helps practitioners and XQuery processor vendors to find performance problems in an XQuery processor.
Combined Therapy With Insulin Plus Oral Agents: Is There Any Advantage? (2008)

P hysicians in many countries usecombinations of antihyperglycemicagents to achieve the best glycemic control possible under the conditions faced by individual patients with type 2 diabetes. This widespread use of com-bined therapies, including oral agents combined with insulin, suggests that the diabetes community accepts the value of this tactic. A routine need for combined therapies was explicitly acknowledged by the investigators in the U.K. Prospective Diabetes Study. Review of the results of 9 years of monotherapy with various agents in the U.K. Prospective Diabetes Study found that fasting plasma glucose (FPG) was kept below 7.8 mmol/l (140 mg/dl) in
MRI feedback temperature control for focused ultrasound surgery (2002)

A temperature feedback controller routine using a physical model for temperature evolution was developed for use with focused ultrasound surgery. The algorithm for the controller was a multi-input, single-output linear quadratic regulator (LQR) derived from Pennes' bioheat transfer equation. The controller was tested with simulated temperature data that had the same characteristics as those obtained with magnetic resonance imaging (MRI). The output of the controller was the appropriate power level to be used by the transducer. Tissue parameters estimated prior to the simulated treatments were used to determine the controller parameters. The controller performance was simulated in three dimensions with varying system parameters, and sufficient temperature tracking was achieved. The worst-case overshoot was 7 degrees C and the steady-state error was 5 degrees C. The simulated behaviour of the controller suggests satisfactory performance and that the controller may be useful in controlling the power output during MRI-monitored ultrasound surgery.
A novel function of Valpha14+CD4+NKT cells: stimulation of IL-12 production by antigen-presenting cells in the innate immune system. (1999)

The balance between Th1 and Th2 development is determined by IL-4 and IL-12. While the role for CD4+ NK1.1+ T (NKT) cells in influencing this balance has been recognized based on their capacity to produce IL-4, it is unknown how IL-12 is produced in the innate immune system in which they participate. This study demonstrates that Ag-activated CD4+ NKT cells express CD40 ligand (CD40L) (CD154), which engages CD40 on APC and stimulates them to produce IL-12. Culture of B cell-depleted spleen cells from C57BL/6 mice with alpha-galactosylceramide (alpha-GalCer) capable of selectively stimulating Valpha14/Jalpha281+ NKT cells resulted in the production of IL-12 together with IFN-gamma and IL-4. alpha-GalCer-induced IL-12 production occurred in I-Abbeta-deficient mice, but not in beta2-microglobulin-deficient and Valpha14/Jalpha281 TCR-deficient mice, and was inhibited by anti-CD40L mAb. Of CD4+ and CD4- NKT cells, the capacity to express CD40L/CD154 and trigger IL-12 production following alpha-GalCer stimulation was exhibited preferentially by the CD4+ NKT subset. IL-12 production was also observed in alpha-GalCer-treated mice. Production of IL-12 preceded IFN-gamma production, and IL-12 was required for IFN-gamma, but not IL-4, production. A stimulatory/inhibitory relationship existed between IL-12 and IL-4 production. These results illustrate a novel function of CD4+ NKT cells that could be involved in the regulation of Th1 vs Th2 development.
The Barnett Shale: Compositional fractionation associated with intraformational petroleum migration, retention, and expulsion (2015)

Author: Han, Yuanjia et al.; Genre: Journal Article; Finally published : 2015; Open Access; Title: The Barnett Shale: Compositional fractionation associated with intraformational petroleum migration, retention and expulsion
Link state routing in wireless ad-hoc networks (2004)

Link state has been the dominating IGP routing technology in IP networks for more than a decade. With the advent of wireless ad-hoc networking, the need for light, efficient and robust routing makes it a good candidate to be also used in this constrained environment. One of the key issue in ad-hoc networking is the lack of bandwidth. Thus, in this paper we examine the overhead due to link state routing in an ad-hoc network. More precisely we study the classic link-state protocol OSPF and OLSR, a link state protocol that was developed specifically for ad-hoc networks. Further, we study how this overhead evolves when the node density increases. The last part of the paper presents directions towards extending OSPF for wireless and ad-hoc networks, which would make it a favorite to seamlessly unify wired and mobile IP networks.
Alkaline phosphatase for treatment of sepsis-induced acute kidney injury: a prospective randomized double-blind placebo-controlled trial (2012)

www.clinicaltrials.gov: NCT00511186.
Intracellular Sequestration of Sodium by a Novel Na+/H+ Exchanger in Yeast Is Enhanced by Mutations in the Plasma Membrane H+-ATPase (1997)

Sodium tolerance in yeast is disrupted by mutations in calcineurin, a Ca2+/calmodulin-dependent protein phosphatase, which is required for modulation of Na+ uptake and efflux mechanisms. Five Na+-tolerant mutants were isolated by selecting for suppressors of calcineurin mutations, and mapped to the PMA1 gene, encoding the plasma membrane H+-ATPase. One mutant, pma1-alpha4, which has the single amino acid change Glu367 --> Lys at a highly conserved site within the catalytic domain of the ATPase, was analyzed in detail to determine the mechanism of Na+ tolerance. After exposure to Na+ in the culture medium, 22Na influx in the pma1 mutant was reduced 2-fold relative to control, consistent with a similar decrease in ATPase activity. Efflux of 22Na from intact cells was relatively unchanged in the pma1 mutant. However, selective permeabilization of the plasma membrane revealed that mutant cells retained up to 80% of intracellular Na+ within a slowly exchanging pool. We show that NHX1, a novel gene homologous to the mammalian NHE family of Na+/H+ exchangers, is required for Na+ sequestration in yeast and contributes to the Na+-tolerant phenotype of pma1-alpha4.
A metal–ion-responsive adhesive material via switching of molecular recognition properties (2014)

Common adhesives stick to a wide range of materials immediately after they are applied to the surfaces. To prevent indiscriminate sticking, smart adhesive materials that adhere to a specific target surface only under particular conditions are desired. Here we report a polymer hydrogel modified with both β-cyclodextrin (βCD) and 2,2'-bipyridyl (bpy) moieties (βCD-bpy gel) as a functional adhesive material responding to metal ions as chemical stimuli. The adhesive property of βCD-bpy gel based on interfacial molecular recognition is expressed by complexation of metal ions to bpy that controlled dissociation of supramolecular cross-linking of βCD-bpy. Moreover, adhesion of βCD-bpy gel exhibits selectivity on the kinds of metal ions, depending on the efficiency of metal-bpy complexes in cross-linking. Transduction of two independent chemical signals (metal ions and host-guest interactions) is achieved in this adhesion system, which leads to the development of highly orthogonal macroscopic joining of multiple objects.
Comparative genomics provides evidence for the 3‐hydroxypropionate autotrophic pathway in filamentous anoxygenic phototrophic bacteria and in hot spring microbial mats (2007)

Stable carbon isotope signatures of diagnostic lipid biomarkers have suggested that Roseiflexus spp., the dominant filamentous anoxygenic phototrophic bacteria inhabiting microbial mats of alkaline siliceous hot springs, may be capable of fixing bicarbonate via the 3-hydroxypropionate pathway, which has been characterized in their distant relative, Chloroflexus aurantiacus. The genomes of three filamentous anoxygenic phototrophic Chloroflexi isolates (Roseiflexus sp. RS-1, Roseiflexus castenholzii and Chloroflexus aggregans), but not that of a non-photosynthetic Chloroflexi isolate (Herpetosiphon aurantiacus), were found to contain open reading frames that show a high degree of sequence similarity to genes encoding enzymes in the C. aurantiacus pathway. Metagenomic DNA sequences from the microbial mats of alkaline siliceous hot springs also contain homologues of these genes that are highly similar to genes in both Roseiflexus spp. and Chloroflexus spp. Thus, Roseiflexus spp. appear to have the genetic capacity for carbon dioxide reduction via the 3-hydroxypropionate pathway. This may contribute to heavier carbon isotopic signatures of the cell components of native Roseiflexus populations in mats compared with the signatures of cyanobacterial cell components, as a similar isotopic signature would be expected if Roseiflexus spp. were participating in photoheterotrophic uptake of cyanobacterial photosynthate produced by the reductive pentose phosphate cycle.
Phase I clinical trial: T‐cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA‐A0201‐specific peptides from prostate‐specific membrane antigen (1996)

BACKGROUND Conventional treatment for metastatic prostate cancer have failed to demonstrate curative potential in all patients. Investigations involving the role of T-cell immunity in the clearance of neoplastic cells are now available. Development of T-cell immunotherapy may give a new approach to the treatment of advanced metastatic prostate cancer. METHODS A phase I clinical trial assessing the administration of autologous dendritic cells (DC) pulsed with HLA-A0201-specific prostate-specific membrane antigen (PSMA) peptides were conducted. Participants were divided into five groups receiving four or five infusions of peptides alone (PSM-P1 or PSM-P2; groups 1 and 2, respectively), autologous DC (group 3), or DC pulsed with PSM-P1 or P2 (groups 4 and 5, respectively). RESULTS No significant toxicity was observed in all five groups. Cellular response against PSM-P1 and -P2 was observed in HLA-A2+ patients infused with DC pulsed with PSM-P1 or -P2 (groups 4 and 5), respectively. An average decrease in PSA was detected only in group 5. Seven partial responders were identified based on NPCP criteria + PSA. CONCLUSIONS Infusions of test substances were well tolerated by all study participants. Detection of cellular response and decrease in PSA level in some patients who received DC pulsed with PSM-P2 indicate this method's potential in prostate cancer therapy. © 1996 Wiley-Liss, Inc.
Understanding the control of Pseudomonas aeruginosa alginate synthesis and the prospects for management of chronic infections in cystic fibrosis (2005)

Decades of research have been dedicated to the study of the opportunistic pathogen Pseudomonas aeruginosa, a Gram-negative, environmental bacterium that secretes the exopolysaccharide alginate during chronic lung infection of cystic fibrosis (CF) patients. Although P. aeruginosa utilizes a variety of factors to establish a successful infection in the lungs of CF patients, alginate has stood out as one of the best-studied prognostic indicators of chronic lung infection. While the genetics, biosynthesis and regulation of alginate are well understood, questions still remain concerning its role in biofilm development and its potential as a therapeutic target. The purpose of this review is to provide a brief summary of alginate biosynthesis and regulation, and to highlight recent discoveries in the areas of alginate production, biofilm formation and vaccine design. This information is placed in context with a proposed P. aeruginosa infectious pathway, highlighting avenues for the use of existing therapies as well as the potential for novel agents to reduce or eliminate chronic infections in CF patients.
Advanced Compiler Design and Implementation (1997)

From the Foreword by Susan L. Graham: This book takes on the challenges of contemporary languages and architectures, and prepares the reader for the new compiling problems that will inevitably arise in the future. The definitive book on advanced compiler design This comprehensive, up-to-date work examines advanced issues in the design and implementation of compilers for modern processors. Written for professionals and graduate students, the book guides readers in designing and implementing efficient structures for highly optimizing compilers for real-world languages. Covering advanced issues in fundamental areas of compiler design, this book discusses a wide array of possible code optimizations, determining the relative importance of optimizations, and selecting the most effective methods of implementation. * Lays the foundation for understanding the major issues of advanced compiler design * Treats optimization in-depth * Uses four case studies of commercial compiling suites to illustrate different approaches to compiler structure, intermediate-code design, and optimization-these include Sun Microsystems's compiler for SPARC, IBM's for POWER and PowerPC, DEC's for Alpha, and Intel's for Pentium an related processors * Presents numerous clearly defined algorithms based on actual cases * Introduces Informal Compiler Algorithm Notation (ICAN), a language devised by the author to communicate algorithms effectively to people
Global distribution of the CCR2-64I/CCR5-59653T HIV-1 disease-protective haplotype (2000)

The greater geographical distribution of the CCR2-64I/CCR5-59653T haplotype compared with that of CCR5-delta32 suggests that it is a much older mutation whose origin predates the dispersal of modern humans.
Mechanism and Kinetics of RAFT-Mediated Graft Polymerization of Styrene on a Solid Surface. 1. Experimental Evidence of Surface Radical Migration (2001)

The mechanism and kinetics of RAFT-mediated graft polymerization of styrene initiated on a silica particle were studied, where RAFT is the reversible addition−fragmentation chain transfer (RAFT) process. To prepare probe graft polymers with a dithiobenzoyl (X) group at the chain end, oligomeric polystyrene (PS) was grafted on a silica particle by the surface-initiated atom transfer radical polymerization (ATRP) technique, and then the terminal halogen atom of the graft polymer was converted to the X group by the reaction with 1-phenylethyl dithiobenzoate in the presence of CuBr/dHbipy complex in toluene. The graft polymerization of styrene on the PS−X-grafted silica particle was carried out in the presence of a free RAFT agent. After the polymerization, the graft chain was cleaved from the silica particle by treatment with HF and characterized. The GPC analysis revealed that the graft polymers, while their Mn increased linearly with increasing monomer conversion, gave a GPC curve with a prominent shoulder assignable to the recombined (dead) polymer. It was proved that the enhanced recombination is specific to the RAFT-mediated graft polymerization and is due to the effective migration of radical on the surface by sequential degenerative (exchange) chain transfer. This is a kind of reaction−diffusion process.
Immunoglobulin‐producing cells in plasma cell orificial mucositis (1989)

Plasma cell orificial mucositis is a benign idiopathic condition of orificial mucous membranes characterized histologically by a dense band-like plasmacytic infiltrate. We studied 8 cases of this disease by immunohistochemical methods for subsets of immunoglobulin-producing cells. The infiltrating plasma cells were found to produce mostly IgG and IgA with the predominance of kappa chain-producing cells over lambda chain-producing cells. This polyclonal plasma cell infiltrate composed of IgG- and IgA-producing cells is in accordance with the pattern observed in the inflammatory infiltrate around certain epidermal neoplasms accompanied by the plasmacytic infiltrate, such as actinic keratosis, Bowen's disease, squamous cell carcinoma, and syringocystadenoma papilliferum.
Multiecho reconstruction for simultaneous water‐fat decomposition and T2* estimation (2007)

The T2*-IDEAL technique has potential applications in imaging of diffuse liver disease for evaluation of both hepatic steatosis and iron overload in a single breath-hold.
Oriented Nanofibrous Polymer Scaffolds Containing Protein‐Loaded Porous Silicon Generated by Spray Nebulization (2018)

Oriented composite nanofibers consisting of porous silicon nanoparticles (pSiNPs) embedded in a polycaprolactone or poly(lactide-co-glycolide) matrix are prepared by spray nebulization from chloroform solutions using an airbrush. The nanofibers can be oriented by an appropriate positioning of the airbrush nozzle, and they can direct growth of neurites from rat dorsal root ganglion neurons. When loaded with the model protein lysozyme, the pSiNPs allow the generation of nanofiber scaffolds that carry and deliver the protein under physiologic conditions (phosphate-buffered saline (PBS), at 37 °C) for up to 60 d, retaining 75% of the enzymatic activity over this time period. The mass loading of protein in the pSiNPs is 36%, and in the resulting polymer/pSiNP scaffolds it is 3.6%. The use of pSiNPs that display intrinsic photoluminescence (from the quantum-confined Si nanostructure) allows the polymer/pSiNP composites to be definitively identified and tracked by time-gated photoluminescence imaging. The remarkable ability of the pSiNPs to protect the protein payload from denaturation, both during processing and for the duration of the long-term aqueous release study, establishes a model for the generation of biodegradable nanofiber scaffolds that can load and deliver sensitive biologics.