gebhart/patrepeval huggingface dataset:
Impact of conjugation chemistry on the immunogenicity of S. Typhimurium conjugate vaccines (2014)

Salmonella Typhimurium is major cause of invasive nontyphoidal Salmonella disease in Africa. Conjugation of S. Typhimurium O-antigen to an appropriate carrier protein constitutes a possible strategy for the development of a vaccine against this disease, for which no vaccines are currently available. The conjugation chemistry used is one of the parameters that can affect the immunogenicity of glycoconjugate vaccines. Herein different glycoconjugates were synthesized to investigate the impact of this variable on the immunogenicity of S. Typhimurium conjugate vaccines in mice, all with CRM₁₉₇ as carrier protein. Random derivatization along the O-antigen chain was compared with site-directed activation of the terminal KDO sugar residue of the core oligosaccharide. In particular, two different random approaches were used, based on the oxidation of the polysaccharide, which differently impact the structure and conformation of the O-antigen chain. For the selective conjugation methods, linkers of two different lengths were compared. When tested in mice, all conjugates induced anti-O-antigen IgG antibodies with serum bactericidal activity. Similar anti-O-antigen antibody levels were elicited independent of the chemistry used and a higher degree of saccharide derivatization did not impact negatively on the anti-O-antigen IgG response. Bactericidal activity of serum antibodies induced by selective conjugates was similar independent of the length of the spacer used. Random conjugates elicited antibodies with greater bactericidal activity than selective ones, and an inverse correlation was found between degree of O-antigen modification and antibody functional activity.
Specific Interaction of Type I Receptors of the TGF-β Family with the Immunophilin FKBP-12 (1994)

Transforming growth factor-beta (TGF-beta) family members bind to receptors that consist of heteromeric serine-threonine kinase subunits (type I and type II). In a yeast genetic screen, the immunophilin FKBP-12, a target of the macrolides FK506 and rapamycin, interacted with the type I receptor for TGF-beta and with other type I receptors. Deletion, point mutation, and co-immunoprecipitation studies further demonstrated the specificity of the interaction. Excess FK506 competed with type I receptors for binding to FKBP-12, which suggests that these receptors share or overlap the macrolide binding site on FKBP-12, and therefore they may represent its natural ligand. The specific interaction between the type I receptors and FKBP-12 suggests that FKBP-12 may play a role in type I receptor-mediated signaling.
Historical data recording for process computers (1981)

Computers have been used to monitor and control chemical and refining processes for more than 15 years. During this time, there has been a steady growth in the variety and sophistication of the functions performed by these process computers. Early systems were limited to maintaining only current operating measurements, available through crude operator's consoles or noisy teletypes. The value of retaining a process history, that is, a collection of measurements over time, became apparent, and early efforts produced shift and daily summary reports. The need for improved process historians which record, retrieve and display process information has grown as process computers assume larger responsibilities in plant operations. This paper describes newly developed process historian functions that have been used on several of its in-house process monitoring and control systems in Du Pont factories. 3 refs.
A 3' enhancer contributes to the stage-specific expression of the human beta-globin gene. (1987)

The human beta-globin and G gamma-globin genes are expressed at different stages of human development and also show distinct temporal patterns of expression when transferred into the mouse germ line. In transgenic mice, the beta-globin gene is expressed only in fetal and adult erythroid cells, whereas the G gamma-globin gene is active only in embryonic erythroid cells. Previous experiments suggested that beta-globin 3' sequences were important for expression in mouse fetal and adult erythroid cells, and in this paper we directly demonstrate the presence of an enhancer in the 3'-flanking region of the gene. First, deletion of sequences between 605 and 895 bp, 3' to the poly(A) site, results in a 10-fold reduction in the average level of expression of the beta-globin gene in transgenic mouse fetal livers. Second, a DNA fragment including beta-globin 3'-flanking sequences [425-1480 bp from the poly(A) site], in either orientation, activates transcription from the otherwise silent G gamma-globin promoter in the mouse fetal liver; DNA sequences between 150 and 730 bp or between 920 and 1680 bp, 3' to the beta-globin gene, are inactive by this assay. Together, these experiments identify an enhancer, in the region approximately 600-900 bp, 3' to the beta-globin poly(A) site, which contributes to the differential stage-specific expression of the beta-globin and G gamma-globin genes.
High level of transgene expression in cell cultures and in the mouse by replication-incompetent adenoviruses harboring modified VAI genes (1997)

Replication-incompetent adenoviruses are currently used in gene therapy trials. Most of the work designed to increase the expression from these vectors concerns the modification of cis sequences of the foreign transcription unit, so as to improve the transcription level or the stability of the mRNA. In this report, we show that an alternative strategy based on the coexpression of modified VAI genes can efficiently increase gene expression both in cell cultures and in animals. The VAI RNA is synthesized mainly during the late phase of the adenovirus cycle and increases the translation of late adenovirus gene products by counteracting the effect of an interferon-induced kinase, the PKR. We have constructed several modified VAI genes in which the central domain was deleted or substituted by exogenous sequences. These modified VAI genes, or the native VAI gene, were cloned into the left part of adenovirus type 5 genomes harboring their own endogenous VAI gene. One of the resulting viruses (Ad-VAr) increased 12.5- to 502-fold the expression level of reporter genes, either expressed as a constitutive cell line from an extrachromosomal DNA or introduced into cells by coinfection with another adenovirus vector. This effect was independent of the promoter, the coding sequence, and the 5' untranslated mRNA sequence and was obvious in the two non-E1-complementing cell lines tested (HeLa and Vero). Coinfection of Ad-VAr with adenoviruses expressing the luciferase gene from the major late promoter or Rous sarcoma virus (RSV) promoter by the intravenous route in mice increased by more than 33 (MLP)- to 128 (RSV)- and 4,700 (MLP)- to 30,000 (RSV)-fold the expression level of the reporter gene in the lungs and liver, respectively. The intramuscular coinoculation of Ad-VAr and Ad-MLP-gD (a recombinant adenovirus vaccine expressing gD from the pseudorabies herpes virus) led to a 10-fold decrease in the protective dose of Ad-gD in mice. Ad-VAfull, a similar adenovirus in which the native VAI gene was cloned at the left part of the genome, showed no evidence of efficacy in cell culture and in mice. These results suggest that the use of modified VAI genes expressed at the early phase of the cycle can be helpful in the design of potent adenovirus vectors.
Direct catalytic asymmetric aldol reactions of pyruvates: scope and mechanism (2004)

The direct aldol reaction of 2-ketoesters catalyzed by chiral bisoxazoline copper(II) complexes has been investigated. First the direct homo-aldol reaction of ethyl pyruvate is reported which proceeds to give diethyl 2-hydroxy-2-methyl-4-oxoglutarate. This was isolated as the more stable optically active isotetronic acid in good yield and enantiomeric excess in the absence of bases such as amines. Detailed investigations of the use of different chiral Lewis acids as the catalyst, amines, ratios of chiral bisoxazoline copper(II) salts:amine, and solvents gave up to 96% ee of the isotetronic acid. Then the reaction was extended to a cross-aldol reaction of various 2-ketoesters with activated carbonyl compounds to give the cross-aldol adduct with excellent enantiomeric excess. Furthermore, the synthesis of the isotetronic acids was investigated from these cross-aldol adducts giving important information about the formation of the stereogenic centers during the aldol reaction. Based on the absolute configuration of the homo-aldol adduct the mechanism for the aldol reaction is discussed.
High performance and flexible imaging Sub-system (2014)

Imaging Sub-system (ISS) enables capturing photographs or live video from raw image sensors. This consists of a set of sensor interfaces and cascaded set of algorithms to improve image/video quality. This paper illustrates typical imaging sub-system architectures consisting of a Sensor front end, an Image Signal Processor (ISP) and an Image Co-processor (sIMCOP). Here we describe the ISS developed by Texas Instruments (TI) for the OMAP 5432 processor. The given solution is flexible to interface with various kinds of image sensors and provides hooks to tune visual quality for specific customers as well as end applications. This solution is also flexible by providing options to enable customized data flows based on actual algorithm needs. The overall solution runs at a high throughput of 1 pixel/clock cycle to enable full HD video at high visual quality.
Divergent regulation of phosphatidylinositol 3-kinase P85 alpha and P85 beta isoforms upon T cell activation (1993)

Phosphatidylinositol (PtdIns) 3-kinase is composed of a catalytic p110 subunit and a regulatory p85 subunit. A synthetic phosphopeptide corresponding to the kinase insert of the human PDGF beta subunit receptor and monoclonal antibodies raised against the two described p85 isoforms, p85 alpha and p85 beta were used to isolate PtdIns 3-kinase from human T lymphocytes. We demonstrate that T cells express both p85 alpha and p85 beta proteins. Both isoforms tightly associate with a p110 protein and with PtdIns 3-kinase activity in T cells. Upon triggering of the T cell antigen receptor (TCR)/CD3 complex or activation of protein kinase C (PKC) the p110 protein complexed to p85 alpha becomes rapidly phosphorylated exclusively on serine residues. p85 alpha does not appear to undergo a change in its basal serine phosphorylation during T cell activation. In contrast, stimulation of the TCR/CD3 complex or PKC, results in a marked and rapid increase in phosphorylation of p85 beta on threonine residues. These data show that PtdIns 3-kinase can be a substrate for serine/threonine kinases in T cells. The differential phosphorylation of p85 alpha and p85 beta reveals the potential for divergent regulation and function of these two PtdIns 3-kinase isoforms during T cell activation.
Post-extrasystolic potentiation without a compensatory pause in normal and diseased hearts. (1990)

Variables derived from left ventricular volume were used to study post-extrasystolic potentiation. Left ventriculograms were obtained from 11 healthy individuals and 49 patients with coronary heart disease (30 with a previous myocardial infarction and 19 without any signs of myocardial damage). Post-extrasystolic potentiation was induced by a regularly driven right atrial rhythm that was interrupted by one atrial extrasystole in such a way that the post-extrasystolic RR interval was kept equal to the basic RR interval. The left ventricular end diastolic volumes of the pre-extrasystolic and post-extrasystolic beats were equal. In all groups there was evidence of post-extrasystolic potentiation in one or more of the indices of left ventricular function (ejection fraction, mean normalised systolic ejection rate, and systolic volume, and stroke volume). Potentiation was especially evident in patients with left ventricular damage; this suggests that a compensating mechanism is an intrinsic property of the myocardium. The Frank-Starling mechanism does not contribute to the increased performance of the post-extrasystolic beat in normal individuals or in patients with coronary artery disease.
Central Mechanisms of Itch (2016)

This chapter summarizes recent findings regarding the central transmission of acute and chronic itch. Itch is transduced by cutaneous pruriceptors that transmit signals to neurons in the superficial spinal cord. Spinal itch-signaling circuits utilize several neuropeptides whose receptors represent novel targets to block itch transmission. Itch is relieved by scratching, which activates spinal interneurons to inhibit itch-transmitting neurons. Spinal itch transmission is also thought to be modulated by descending pathways. Itch is transmitted rostrally via ascending pathways to activate a variety of brain regions involved in sensory discrimination of affective and motor responses to itch. The pathophysiological mechanisms of chronic itch are poorly understood but likely involve sensitization of itch-signaling pathways and/or dysfunction of itch-inhibitory circuits. Improved understanding of central itch mechanisms has identified a number of novel targets for the development of antipruritic treatment strategies.
Analysis of the interaction between the bacterial superantigen streptococcal pyrogenic exotoxin A (SpeA) and the human T‐cell receptor (1997)

Streptococcus pyogenes that produces the bacterial superantigen streptococcal pyrogenic exotoxin A (SpeA) is associated with outbreaks of streptococcal toxic shock syndrome (STSS) in the United States and Europe. SpeA stimulates V beta 2.1, 12.2, 14.1, and 15.1-positive T cells, and the lymphokine production from the activated T cells is believed to result in the symptoms associated with STSS. The T-cell receptor (TCR)-SpeA interaction is crucial for superantigenic activity, and studies were undertaken to determine regions of both SpeA and the TCR involved in the formation of MHC/SpeA/TCR complexes. Previously, recombinant toxins encoded by speA alleles 1, 2, and 3 as well as toxins resulting from 19 distinct point mutations in speA1 were generated. Here, these 22 toxin forms were incubated with human peripheral blood mononuclear cells (PBMCs), and the percentages of T-cell blasts bearing V beta chains 2.1, 12.2, and 14.1 were quantified by flow cytometry. The analysis indicates that the residues of SpeA needed for a productive TCR interaction differ for each V beta chain examined. An amino acid substitution at only one site significantly affected the toxin's ability to stimulate V beta 2.1-expressing T cells, three individual amino acid substitutions resulted in significant loss of ability to stimulate V beta 12.2-expressing T cells, and substitution at 13 individual sites significantly affected the ability to stimulate V beta 14.1-expressing T cells. To elucidate the regions of the V beta chains that interacted with SpeA, synthetic peptides representative of the human V beta 12.2 complementary-determining regions (CDRs) 1, 2, and 4 were used to block the SpeA-mediated proliferation of human PBMCs. The CDR1, CDR2 and CDR4 peptides were each able to block proliferation, with the activity of CDR1 > CDR2 > CDR4. Combinations of CDR1 peptide with CDR2 or CDR4 peptides allosterically enhanced the ability of each to block proliferation, suggesting SpeA has distinct binding sites for the CDR loops.
Chronic myeloid leukemia: 2016 update on diagnosis, therapy, and monitoring (2016)

CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson gene (ABL1) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR-ABL1 fusion oncogene, which in turn translates into a BCR-ABL oncoprotein. Frontline therapy: Three tyrosine kinase inhibitors (TKIs), imatinib, nilotinib, and dasatinib are approved by the United States Food and Drug Administration for first-line treatment of patients with newly diagnosed CML in chronic phase (CML-CP). Clinical trials with 2nd generation TKIs reported significantly deeper and faster responses; their impact on long-term survival remains to be determined. Salvage therapy: For patients who fail frontline therapy, second-line options include second and third generation TKIs. Although second and third generation TKIs are potent and selective TKIs, they exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities, disease stage, and BCR-ABL1 mutational status. Patients who develop the T315I "gatekeeper" mutation display resistance to all currently available TKIs except ponatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML-CP who have failed at least two TKIs, and for all patients in advanced phase disease.
Wound Microbiology and Associated Approaches to Wound Management (2001)

The majority of dermal wounds are colonized with aerobic and anaerobic microorganisms that originate predominantly from mucosal surfaces such as those of the oral cavity and gut. The role and significance of microorganisms in wound healing has been debated for many years. While some experts consider the microbial density to be critical in predicting wound healing and infection, others consider the types of microorganisms to be of greater importance. However, these and other factors such as microbial synergy, the host immune response, and the quality of tissue must be considered collectively in assessing the probability of infection. Debate also exists regarding the value of wound sampling, the types of wounds that should be sampled, and the sampling technique required to generate the most meaningful data. In the laboratory, consideration must be given to the relevance of culturing polymicrobial specimens, the value in identifying one or more microorganisms, and the microorganisms that should be assayed for antibiotic susceptibility. Although appropriate systemic antibiotics are essential for the treatment of deteriorating, clinically infected wounds, debate exists regarding the relevance and use of antibiotics (systemic or topical) and antiseptics (topical) in the treatment of nonhealing wounds that have no clinical signs of infection. In providing a detailed analysis of wound microbiology, together with current opinion and controversies regarding wound assessment and treatment, this review has attempted to capture and address microbiological aspects that are critical to the successful management of microorganisms in wounds.
Beamspace MIMO for high-dimensional multiuser communication at millimeter-wave frequencies (2013)

Millimeter-wave (mm-wave) systems operating from 30-300GHz provide a unique opportunity for meeting the exploding capacity demands on wireless networks. In addition to orders-of-magnitude larger bandwidths, the small wavelengths at mm-wave enable high-dimensional multiple-input multiple-output (MIMO) operation. However, fully exploiting the advantages of mm-wave requires prohibitively high transceiver complexity when using conventional MIMO techniques. In this paper we propose and analyze the sum capacity of several linear, reduced-complexity multiuser MIMO (MU-MIMO) precoders that exploit the concept of beamspace MIMO (B-MIMO) communication - multiplexing data onto orthogonal spatial beams that serve as approximate channel eigenfunctions. Due to quasi-optical propagation at mm-wave, MIMO channels are expected to be low-rank and the low channel rank is manifested in the sparsity of the beamspace channel matrix. This enables near-optimal rank and complexity reduction via the concept of multi-beam selection. We present numerical capacity results that demonstrate the reduced-complexity B-MIMO precoders are able to closely approximate the performance of their full-dimensional counterparts with complexity that tracks the number of mobile stations (MSs). In mm-wave systems, where the number of MSs is expected to be much lower than the system dimension, this enables a considerable reduction in the digital signal processing complexity and in systems equipped with analog beamforming front-ends the hardware complexity is also reduced. Thus, the proposed reduced-complexity multiuser precoders provide a near-optimal route for achieving multi-Gigabit/s sum rates in mm-wave MU-MIMO networks with the lowest transceiver complexity.
Paf‐acether‐induced death in mice: involvement of arachidonate metabolites and β‐adrenoceptors (1987)

Intravenous Paf‐acether (Paf, 15–80 μg kg −1 ) killed conscious Swiss mice in a dose‐dependent manner, without causing platelet aggregation in the lung micro vasculature, or pulmonary oedema. Propranolol (0.01–10 mg kg −1 , i.p.) potentiated the effects of an LD 20 of Paf dose‐dependently, while the β 1 ‐adrenoceptor selective antagonist, metoprolol, was three orders of magnitude less potent in this respect. Salbutamol (1 mg kg −1 , i.p.) provided complete protection against an LD 80 of Paf. High doses of indomethacin, aspirin, benoxaprofen and FPL 55712 given i.p. failed to inhibit the effects of an LD 80 of Paf, while BW 755C (50–100 mg kg −1 ) exerted a dose‐dependent protection and benzydamine (50 mg kg −1 ) and nordihydroguaiaretic acid (200 mg kg −1 ) were partially active. Dexamethasone (1–5 mg kg −1 , s.c.) exerted a dose‐dependent protection, when administered at least 4h before Paf. In mice anaesthetized with urethane, Paf (1–30 μg kg −1 ) produced hypotension which was not clearly dose‐related. The effects of the highest dose were also tested on the resistance of the lungs to inflation and found to produce bronchoconstriction. It may be concluded that pharmacological manipulation of β 2 ‐adrenoceptors modulates Paf‐induced death in mice, while arachidonate metabolites of the cyclo‐oxygenase pathway and peptidoleukotrienes do not appear to be involved. However, lipoxygenase products, distinct from peptidoleukotrienes, may play a role in this phenomenon. It is suggested that bronchoconstriction, probably associated with cardiovascular effects, is a major determinant of the acute toxicity of Paf in mice.
Neuroendocrine-immunity in patients with Alzheimer's disease: toward translational epigenetics (2007)

The emerging domain of epigenetics in molecular medicine finds application for a variety of patient populations. Here, we present fundamental neuroendocrine immune evidence obtained in patients with senile dementia of the Alzheimer's type (sDAT), and discuss the implications of these data from the viewpoint of translational epigenetics of Alzheimer's disease. We followed 18 subjects with mild sDAT treated with acetylcholinesterase inhibitors, and 10 control subjects matched for age in a repeated measure design every six months for 18 months. We monitored psychosocial profile (Mini-Mental State Examination, Functional Assessment Staging, Independence in Activities of Daily Living, Depression, Profile of Moods States) in parallel to immunophenotypic parameters of T cell subpopulations by flow cytometry. Based on change in the mini-mental state score at entry and at 18 months, patients with sDAT were assigned to a "fast progression" (delta greater than 2 points) or to a "slow progression" group (delta less than or equal to 2 points). The change in circulating activated T cells (CD3+Dr+) with time in patients with sDAT was significantly inversely correlated with the change in time in natural killer (NK) cytotoxic activity to cortisol modulation in these patients, which was greater in patients with fast progression, compared to slow progression sDAT. These data indicate underlying neuroendocrine immune processes during progression of sDAT. Our observations suggest that psychoimmune measures such as those we have monitored in this study provide relevant information about the evolving physiological modulation in patients with sDAT during progression of Alzheimer's disease, and point to new or improved translational epigenetic treatment interventions.